Journal Cover Advanced Drug Delivery Reviews
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   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0169-409X
   Published by Elsevier Homepage  [3123 journals]
  • Technological strategies to overcome the mucus barrier in mucosal drug
           delivery
    • Authors: José das Neves; Bruno Sarmento
      Pages: 1 - 2
      Abstract: Publication date: 15 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 124
      Author(s): José das Neves, Bruno Sarmento


      PubDate: 2018-02-15T09:46:58Z
      DOI: 10.1016/j.addr.2018.01.014
      Issue No: Vol. 124 (2018)
       
  • The biology of mucus: Composition, synthesis and organization
    • Authors: Rama Bansil; Bradley S. Turner
      Pages: 3 - 15
      Abstract: Publication date: 15 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 124
      Author(s): Rama Bansil, Bradley S. Turner
      In this review we discuss mucus, the viscoelastic secretion from goblet or mucous producing cells that lines the epithelial surfaces of all organs exposed to the external world. Mucus is a complex aqueous fluid that owes its viscoelastic, lubricating and hydration properties to the glycoprotein mucin combined with electrolytes, lipids and other smaller proteins. Electron microscopy of mucosal surfaces reveals a highly convoluted surface with a network of fibers and pores of varying sizes. The major structural and functional component, mucin is a complex glycoprotein coded by about 20 mucin genes which produce a protein backbone having multiple tandem repeats of Serine, Threonine (ST repeats) where oligosaccharides are covalently O-linked. The N- and C-terminals of this apoprotein contain other domains with little or no glycosylation but rich in cysteines leading to dimerization and further multimerization via SS bonds. The synthesis of this complex protein starts in the endoplasmic reticulum with the formation of the apoprotein and is further modified via glycosylation in the cis and medial Golgi and packaged into mucin granules via Ca2+ bridging of the negative charges on the oligosaccharide brush in the trans Golgi. The mucin granules fuse with the plasma membrane of the secretory cells and following activation by signaling molecules release Ca2+ and undergo a dramatic change in volume due to hydration of the highly negatively charged polymer brush leading to exocytosis from the cells and forming the mucus layer. The rheological properties of mucus and its active component mucin and its mucoadhesivity are briefly discussed in light of their importance to mucosal drug delivery.
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      PubDate: 2018-02-15T09:46:58Z
      DOI: 10.1016/j.addr.2017.09.023
      Issue No: Vol. 124 (2018)
       
  • A slippery slope: On the origin, role and physiology of mucus
    • Authors: Farhan Taherali; Felipe Varum; Abdul W. Basit
      Pages: 16 - 33
      Abstract: Publication date: 15 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 124
      Author(s): Farhan Taherali, Felipe Varum, Abdul W. Basit
      The mucosa of the gastrointestinal tract, eyes, nose, lungs, cervix and vagina is lined by epithelium interspersed with mucus-secreting goblet cells, all of which contribute to their unique functions. This mucus provides an integral defence to the epithelium against noxious agents and pathogens. However, it can equally act as a barrier to drugs and delivery systems targeting epithelial passive and active transport mechanisms. This review highlights the various mucins expressed at different mucosal surfaces on the human body, and their role in creating a mucoid architecture to protect epithelia with specialized functions. Various factors compromising the barrier properties of mucus have been discussed, with an emphasis on how disease states and microbiota can alter the physical properties of mucus. For instance, Akkermansia muciniphila, a bacterium found in higher levels in the gut of lean individuals induces the production of a thickened gut mucus layer. The aims of this article are to elucidate the different physiological, biochemical and physical properties of bodily mucus, a keen appreciation of which will help circumvent the slippery slope of challenges faced in achieving effective mucosal drug and gene delivery.
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      PubDate: 2018-02-15T09:46:58Z
      DOI: 10.1016/j.addr.2017.10.014
      Issue No: Vol. 124 (2018)
       
  • Mucus models to evaluate the diffusion of drugs and particles
    • Authors: Jaclyn Y. Lock; Taylor L. Carlson; Rebecca L. Carrier
      Pages: 34 - 49
      Abstract: Publication date: 15 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 124
      Author(s): Jaclyn Y. Lock, Taylor L. Carlson, Rebecca L. Carrier
      Mucus is a complex hydrogel that acts as a natural barrier to drug delivery at different mucosal surfaces including the respiratory, gastrointestinal, and vaginal tracts. To elucidate the role mucus plays in drug delivery, different in vitro, in vivo, and ex vivo mucus models and techniques have been utilized. Drug and drug carrier diffusion can be studied using various techniques in either isolated mucus gels or mucus present on cell cultures and tissues. The species, age, and potential disease state of the animal from which mucus is derived can all impact mucus composition and structure, and therefore impact drug and drug carrier diffusion. This review provides an overview of the techniques used to characterize drug and drug carrier diffusion, and discusses the advantages and disadvantages of the different models available to highlight the information they can afford.
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      PubDate: 2018-02-15T09:46:58Z
      DOI: 10.1016/j.addr.2017.11.001
      Issue No: Vol. 124 (2018)
       
  • The role of mucus in cell-based models used to screen mucosal drug
           delivery
    • Authors: Anna Lechanteur; José das Neves; Bruno Sarmento
      Pages: 50 - 63
      Abstract: Publication date: 15 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 124
      Author(s): Anna Lechanteur, José das Neves, Bruno Sarmento
      The increasing interest in developing tools to predict drug absorption through mucosal surfaces is fostering the establishment of epithelial cell-based models. Cell-based in vitro techniques for drug permeability assessment are less laborious, cheaper and address the concerns of using laboratory animals. Simultaneously, in vitro barrier models that thoroughly simulate human epithelia or mucosae may provide useful data to speed up the entrance of new drugs and new drug products into the clinics. Nevertheless, standard cell-based in vitro models that intend to reproduce epithelial surfaces often discard the role of mucus in influencing drug permeation/absorption. Biomimetic models of mucosae in which mucus production has been considered may not be able to fully reproduce the amount and architecture of mucus, resulting in biased characterization of permeability/absorption. In these cases, artificial mucus may be used to supplement cell-based models but still proper identification and quantification are required. In this review, considerations regarding the relevance of mucus in the development of cell-based epithelial and mucosal models mimicking the gastro-intestinal tract, the cervico-vaginal tract and the respiratory tract, and the impact of mucus on the permeability mechanisms are addressed. From simple epithelial monolayers to more complex 3D structures, the impact of the presence of mucus for the extrapolation to the in vivo scenario is critically analyzed. Finally, an overview is provided on several techniques and methods to characterize the mucus layer over cell-based barriers, in order to intimately reproduce human mucosal layer and thereby, improve in vitro/in vivo correlation.
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      PubDate: 2018-02-15T09:46:58Z
      DOI: 10.1016/j.addr.2017.07.019
      Issue No: Vol. 124 (2018)
       
  • The role of mucus on drug transport and its potential to affect
           therapeutic outcomes
    • Authors: Xabier Murgia; Brigitta Loretz; Olga Hartwig; Marius Hittinger; Claus-Michael Lehr
      Pages: 82 - 97
      Abstract: Publication date: 15 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 124
      Author(s): Xabier Murgia, Brigitta Loretz, Olga Hartwig, Marius Hittinger, Claus-Michael Lehr
      A layer of mucus covers the surface of all wet epithelia throughout the human body. Mucus is a hydrogel mainly composed of water, mucins (glycoproteins), DNA, proteins, lipids, and cell debris. This complex composition yields a tenacious viscoelastic hydrogel that lubricates and protects the exposed epithelia from external threats and enzymatic degradation. The natural protective role of mucus is nowadays acknowledged as a major barrier to be overcome in non-invasive drug delivery. The heterogeneity of mucus components offers a wide range of potential chemical interaction sites for macromolecules, while the mesh-like architecture given to mucus by the intermolecular cross-linking of mucin molecules results in a dense network that physically, and in a size-dependent manner, hinders the diffusion of nanoparticles through mucus. Consequently, drug diffusion, epithelial absorption, drug bioavailability, and ultimately therapeutic outcomes of mucosal drug delivery can be attenuated.
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      PubDate: 2018-02-15T09:46:58Z
      DOI: 10.1016/j.addr.2017.10.009
      Issue No: Vol. 124 (2018)
       
  • Chemical modification of drug molecules as strategy to reduce interactions
           with mucus
    • Authors: Francisca Araújo; Cláudia Martins; Cláudia Azevedo; Bruno Sarmento
      Pages: 98 - 106
      Abstract: Publication date: 15 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 124
      Author(s): Francisca Araújo, Cláudia Martins, Cláudia Azevedo, Bruno Sarmento
      Many drug molecules possess inadequate physical-chemical characteristics that prevent to surpass the viscous mucus layer present in the surface of mucosal tissues. Due to mucus protective role and its fast turnover, these drug molecules end up being removed from the body before being absorbed and, thus, before exerting any physiologic affect. Envisaging a better pharmacokinetics profile, chemical modifications, to render drug a more mucopenetrating character, have been introduced to drug molecules backbone towards more effective therapies. Mucus penetration increases when drug molecules are provided with net-neutral charge, when they are conjugated with mucolytic agents and through modifications that makes them resistant to enzymes present in mucus, with the overall increase of their hydrophilicity and the decrease of their molecular weight. All of these characteristics act as a whole and influence each other so they must be well thought when drug molecules are being designed for mucosal delivery.
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      PubDate: 2018-02-15T09:46:58Z
      DOI: 10.1016/j.addr.2017.09.020
      Issue No: Vol. 124 (2018)
       
  • The role of mucus as an invisible cloak to transepithelial drug delivery
           by nanoparticles
    • Authors: María García-Díaz; Ditlev Birch; Feng Wan; Hanne Mørck Nielsen
      Pages: 107 - 124
      Abstract: Publication date: 15 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 124
      Author(s): María García-Díaz, Ditlev Birch, Feng Wan, Hanne Mørck Nielsen
      Mucosal administration of drugs and drug delivery systems has gained increasing interest. However, nanoparticles intended to protect and deliver drugs to epithelial surfaces require transport through the surface-lining mucus. Translation from bench to bedside is particularly challenging for mucosal administration since a variety of parameters will influence the specific barrier properties of the mucus including the luminal fluids, the microbiota, the mucus composition and clearance rate, and the condition of the underlying epithelia. Besides, after administration, nanoparticles interact with the mucosal components, forming a biomolecular corona that modulates their behavior and fate after mucosal administration. These interactions are greatly influenced by the nanoparticle properties, and therefore different designs and surface-engineering strategies have been proposed. Overall, it is essential to evaluate these biomolecule-nanoparticle interactions by complementary techniques using complex and relevant mucus barrier matrices.
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      PubDate: 2018-02-15T09:46:58Z
      DOI: 10.1016/j.addr.2017.11.002
      Issue No: Vol. 124 (2018)
       
  • PEGylation for enhancing nanoparticle diffusion in mucus
    • Authors: Justin T. Huckaby; Samuel K. Lai
      Pages: 125 - 139
      Abstract: Publication date: 15 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 124
      Author(s): Justin T. Huckaby, Samuel K. Lai
      The viscoelastic mucus secretions coating exposed organs such as the lung airways and the female reproductive tract can trap and quickly eliminate not only foreign pathogens and ultrafine particles but also particle-based drug delivery systems, thus limiting sustained and targeted drug delivery at mucosal surfaces. To improve particle distribution across the mucosa and enhance delivery to the underlying epithelium, many investigators have sought to develop nanoparticles capable of readily traversing mucus. The first synthetic nanoparticles shown capable of rapidly penetrating physiological mucus secretions utilized a dense coating of polyethylene glycol (PEG) covalently grafted onto the surface of preformed polymeric nanoparticles. In the decade since, PEG has become the gold standard in engineering mucus-penetrating drug carriers for sustained and targeted drug delivery to the lungs, gastrointestinal tract, eyes, and female reproductive tract. This review summarizes the history of the development of various PEG-based mucus-penetrating particles, and highlights the key physicochemical properties of PEG coatings and PEGylation strategies to achieve muco-inert PEG coatings on nanoparticle drug carriers for improved drug and gene delivery at mucosal surfaces.
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      PubDate: 2018-02-15T09:46:58Z
      DOI: 10.1016/j.addr.2017.08.010
      Issue No: Vol. 124 (2018)
       
  • Beyond PEGylation: Alternative surface-modification of nanoparticles with
           mucus-inert biomaterials
    • Authors: Vitaliy V. Khutoryanskiy
      Pages: 140 - 149
      Abstract: Publication date: 15 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 124
      Author(s): Vitaliy V. Khutoryanskiy
      Mucus is a highly hydrated viscoelastic gel present on various moist surfaces in our body including the eyes, nasal cavity, mouth, gastrointestinal, respiratory and reproductive tracts. It serves as a very efficient barrier that prevents harmful particles, viruses and bacteria from entering the human body. However, the protective function of the mucus also hampers the diffusion of drugs and nanomedicines, which dramatically reduces their efficiency. Functionalisation of nanoparticles with low molecular weight poly(ethylene glycol) (PEGylation) is one of the strategies to enhance their penetration through mucus. Recently a number of other polymers were explored as alternatives to PEGylation. These alternatives include poly(2-alkyl-2-oxazolines), polysarcosine, poly(vinyl alcohol), other hydroxyl-containing non-ionic water-soluble polymers, zwitterionic polymers (polybetaines) and mucolytic enzymes. This review discusses the studies reporting the use of these polymers or potential application to facilitate mucus permeation of nanoparticles.
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      PubDate: 2018-02-15T09:46:58Z
      DOI: 10.1016/j.addr.2017.07.015
      Issue No: Vol. 124 (2018)
       
  • Engineering nanomaterials to overcome the mucosal barrier by modulating
           surface properties
    • Authors: Lei Wu; Wei Shan; Zhirong Zhang; Yuan Huang
      Pages: 150 - 163
      Abstract: Publication date: 15 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 124
      Author(s): Lei Wu, Wei Shan, Zhirong Zhang, Yuan Huang
      Although nanotechnology has been investigated during recent years to increase the bioavailability and therapeutic effects of mucosal administrated drugs, numerous barriers (e.g., pH environment, enzymes and mucus) still limit the delivery efficiency. And the epithelium would also affect the systemic mucosal drug delivery. Amongst all the barriers, the protective mucus has drawn more and more attention, which strongly hinders the accessibility of nanovehicles to epithelium. Therefore, trials to conquer the mucus barrier have been designed using two controversial strategies: mucoadhesion and mucus-penetration. This review summarizes the influence of mucus layer on nanomaterials and introduces the modification strategies by modulating surface properties (i.e., hydrophilicity/hydrophobicity and surface charge) to overcome mucus barriers. Furthermore, it also reviews advanced modification methods to meet the different surface requirements of nanovehicles to overcome mucus and epithelium barriers in systemic mucosal delivery.
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      PubDate: 2018-02-15T09:46:58Z
      DOI: 10.1016/j.addr.2017.10.001
      Issue No: Vol. 124 (2018)
       
  • Enzyme decorated drug carriers: Targeted swords to cleave and overcome the
           mucus barrier
    • Authors: Claudia Menzel; Andreas Bernkop-Schnürch
      Pages: 164 - 174
      Abstract: Publication date: 15 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 124
      Author(s): Claudia Menzel, Andreas Bernkop-Schnürch
      The use of mucus permeating drug carrier systems being able to overcome the mucus barrier can lead to a remarkable enhancement in bioavailability. One promising approach is the design of mucolytic enzyme decorated carrier systems (MECS). These systems include micro- and nanoparticles as well as self-emulsifying drug delivery systems (SEDDS) decorated with mucin cleaving enzymes such as papain (PAP) or bromelain (BRO). MECS are able to cross the mucus barrier in a comparatively efficient manner by cleaving mucus substructures in front of them on their way to the epithelium. Thereby these enzymes hydrolyze peptide bonds of mucus glycoproteins forming tiny holes or passages through the mucus. In various in vitro and in vivo studies MECS proved to be superior in their mucus permeating properties over nanocarriers without enzyme decoration. PAP decorated nanoparticles, for instance, remained 3h after oral administration to an even 2.5-fold higher extend in rat small intestine than the corresponding undecorated nanoparticles permeating the intestinal mucus gel layer to a much lower degree. As MECS break up the mucus network only locally without destroying its overall protective barrier function, even long term treatments with such systems seem feasible. Within this review article we address different drug carrier systems decorated with various types of enzymes, their particular pros and cons and potential applications.
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      PubDate: 2018-02-15T09:46:58Z
      DOI: 10.1016/j.addr.2017.10.004
      Issue No: Vol. 124 (2018)
       
  • No title
    • Authors: Furka
      Abstract: Publication date: Available online 13 February 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Árpád Furka


      PubDate: 2018-02-15T09:46:58Z
       
  • Nanomedicines and gene therapy for the delivery of growth factors to
           improve perfusion and oxygenation in wound healing
    • Authors: Céline M. Desmet; Véronique Préat; Bernard Gallez
      Abstract: Publication date: Available online 12 February 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Céline M. Desmet, Véronique Préat, Bernard Gallez
      Oxygen plays a key role in wound healing, and hypoxia is a major cause of wound healing impairment; therefore, treatments to improve hemodynamics and increase wound oxygenation are of particular interest for the treatment of chronic wounds. This article describes the roles of oxygen and angiogenesis in wound healing as well as the tools used to evaluate tissue oxygenation and perfusion and then presents a review of nanomedicines and gene therapies designed to improve perfusion and oxygenation and accelerate wound healing.
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      PubDate: 2018-02-15T09:46:58Z
      DOI: 10.1016/j.addr.2018.02.001
       
  • Combined use of nanocarriers and physical methods for percutaneous
           penetration enhancement
    • Authors: Nina Dragicevic; Howard Maibach
      Abstract: Publication date: Available online 6 February 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Nina Dragicevic, Howard Maibach
      Dermal and transdermal drug delivery (due to its non-invasiveness, avoidance of the first-pass metabolism, controlling the rate of drug input over a prolonged time, etc.) have gained significant acceptance. Several methods are employed to overcome the permeability barrier of the skin, improving drug penetration into/through skin. Among chemical penetration enhancement methods, nanocarriers have been extensively studied. When applied alone, nanocarriers mostly deliver drugs to skin and can be used to treat skin diseases. To achieve effective transdermal drug delivery, nanocarriers should be applied with physical methods, as they act synergistically in enhancing drug penetration. This review describes combined use of frequently used nanocarriers (liposomes, novel elastic vesicles, lipid-based and polymer-based nanoparticles and dendrimers) with the most efficient physical methods (microneedles, iontophoresis, ultrasound and electroporation) and demonstrates superiority of the combined use of nanocarriers and physical methods in drug penetration enhancement compared to their single use.
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      PubDate: 2018-02-15T09:46:58Z
      DOI: 10.1016/j.addr.2018.02.003
       
  • Scarring vs. functional healing: Matrix-based strategies to regulate
           tissue repair
    • Authors: Timothy J. Keane; Christine-Maria Horejs; Molly M. Stevens
      Abstract: Publication date: Available online 6 February 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Timothy J. Keane, Christine-Maria Horejs, Molly M. Stevens
      All vertebrates possess mechanisms to restore damaged tissues with outcomes ranging from regeneration to scarring. Unfortunately, the mammalian response to tissue injury most often culminates in scar formation. Accounting for nearly 45% of deaths in the developed world, fibrosis is a process that stands diametrically opposed to functional tissue regeneration. Strategies to improve wound healing outcomes therefore require methods to limit fibrosis. Wound healing is guided by precise spatiotemporal deposition and remodelling of the extracellular matrix (ECM). The ECM, comprising the non-cellular component of tissues, is a signaling depot that is differentially regulated in scarring and regenerative healing. This Review focuses on the importance of the native matrix components during mammalian wound healing alongside a comparison to scar-free healing and then presents an overview of matrix-based strategies that attempt to exploit the role of the ECM to improve wound healing outcomes.
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      PubDate: 2018-02-15T09:46:58Z
      DOI: 10.1016/j.addr.2018.02.002
       
  • Integrins in wound healing, fibrosis and tumor stroma: High potential
           targets for therapeutics and drug delivery
    • Authors: Jonas Schnittert; Ruchi Bansal; Gert Storm; Jai Prakash
      Abstract: Publication date: Available online 4 February 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Jonas Schnittert, Ruchi Bansal, Gert Storm, Jai Prakash
      Wound healing is a complex process, which ultimately leads to fibrosis if not repaired well. Pathologically very similar to fibrosis is the tumor stroma, found in several solid tumors which are regarded as wounds that do not heal. Integrins are heterodimeric surface receptors which control various physiological cellular functions. Additionally, integrins also sense ECM-induced extracellular changes during pathological events, leading to cellular responses, which influence ECM remodeling. The purpose and scope of this review is to introduce integrins as key targets for therapeutics and drug delivery within the scope of wound healing, fibrosis and the tumor stroma. This review provides a general introduction to the biology of integrins including their types, ligands, and meaαns of signaling and interaction with growth factor receptors. Furthermore, we highlight integrins as key targets for therapeutics and drug delivery, based on their biological role, expression pattern within human tissues and at cellular level. Next, therapeutic approaches targeting integrins, with a focus on clinical studies, and targeted drug delivery strategies based on αligands are described.
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      PubDate: 2018-02-05T09:38:17Z
      DOI: 10.1016/j.addr.2018.01.020
       
  • Ocular translational science: A review of development steps and paths
    • Authors: Brenda K. Mann; Darren L. Stirland; Hee-Kyoung Lee; Barbara M. Wirostko
      Abstract: Publication date: Available online 4 February 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Brenda K. Mann, Darren L. Stirland, Hee-Kyoung Lee, Barbara M. Wirostko
      Developing successful drug delivery methods is challenging for any tissue, and the eye is no exception. Translating initial concepts into advanced technologies treating diseases in preclinical models and finally into functional and marketable products for humans can be particularly daunting. While referring to specific ophthalmic companies and products, this review considers key exchanges that lead to successful translation. By building on basic science discoveries in the academic setting, applied science can perform proof-of-concept work with simple, benchtop experiments. Eventually, simple models need to be translated to more robust ones where cells, tissues, and entire organisms are incorporated. Successful translation also includes performing due diligence of the intellectual property, understanding the market needs, undertaking clinical development, meeting regulatory requirements, and eventually scale up manufacturing. Different stages of the translation can occur in different environments, including moving from academia to industry, from one company to another, or between veterinary and human applications. The translation process may also rely on contract organizations to move through the complex landscape. While the path to a commercial, marketable product may not look the same each time, it is important to design a development plan with clear goals and milestones to keep on track.
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      PubDate: 2018-02-05T09:38:17Z
      DOI: 10.1016/j.addr.2018.01.012
       
  • Clinical applications of the CellSearch platform in cancer patients
    • Authors: Sabine Riethdorf; Linda O'Flaherty; Claudia Hille; Klaus Pantel
      Abstract: Publication date: Available online 2 February 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Sabine Riethdorf, Linda O'Flaherty, Claudia Hille, Klaus Pantel
      The CellSearch® system (CS) enables standardized enrichment and enumeration of circulating tumor cells (CTCs) that are repeatedly assessable via non-invasive “liquid biopsy”. While the association of CTCs with poor clinical outcome for cancer patients has clearly been demonstrated in numerous clinical studies, utilizing CTCs for the identification of therapeutic targets, stratification of patients for targeted therapies and uncovering mechanisms of resistance is still under investigation. Here, we comprehensively review the current benefits and drawbacks of clinical CTC analyses for patients with metastatic and non-metastatic tumors. Furthermore, the review focuses on approaches beyond CTC enumeration that aim to uncover therapeutically relevant antigens, genomic aberrations, transcriptional profiles and epigenetic alterations of CTCs at a single cell level. This characterization of CTCs may shed light on the heterogeneity and genomic landscapes of malignant tumors, an understanding of which is highly important for the development of new therapeutic strategies.
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      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.011
       
  • Fluorescence anisotropy imaging in drug discovery
    • Authors: Claudio Vinegoni; Paolo Fumene Feruglio; Ignacy Gryczynski; Ralph Mazitschek; Ralph Weissleder
      Abstract: Publication date: Available online 2 February 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Claudio Vinegoni, Paolo Fumene Feruglio, Ignacy Gryczynski, Ralph Mazitschek, Ralph Weissleder
      Non-invasive measurement of drug-target engagement can provide critical insights in the molecular pharmacology of small molecule drugs. Fluorescence polarization/fluorescence anisotropy measurements are commonly employed in protein/cell screening assays. However, the expansion of such measurements to the in vivo setting have proven difficult until recently. With the advent of high-resolution fluorescence anisotropy microscopy it is now possible to perform kinetic measurements of intracellular drug distribution and target engagement in commonly used mouse models. In this review we discuss the background, current advances and future perspectives in intravital fluorescence anisotropy measurements to derive pharmacokinetic and pharmacodynamic measurements in single cells and whole organs.
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      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.019
       
  • Wound healing in the eye: Therapeutic prospects
    • Authors: Mohammed Ziaei; Carol Greene; Colin R. Green
      Abstract: Publication date: Available online 31 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Mohammed Ziaei, Carol Greene, Colin R. Green
      In order to maintain a smooth optical surface the corneal epithelium has to continuously renew itself so as to maintain its function as a barrier to fluctuating external surroundings and various environmental insults. After trauma, the cornea typically re-epithelializes promptly thereby minimizing the risk of infection, opacification or perforation. A persistent epithelial defect (PED) is usually referred to as a non-healing epithelial lesion after approximately two weeks of treatment with standard therapies to no avail. They occur following exposure to toxic agents, mechanical injury, and ocular surface infections and are associated with significant clinical morbidity in patients, resulting in discomfort or visual loss. In the case of deeper corneal injury and corneal pathology the wound healing cascade can also extend to the corneal stroma, the layer below the epithelium. Although significant progress has been made in recent years, pharmaco-therapeutic agents that promote corneal healing remain limited. This article serves as a review of current standard therapies, recently introduced alternative therapies gaining in popularity, and a look into the newest developments into ocular wound healing.
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      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.006
       
  • Enhancing patient-level clinical data access to improve trial outcomes,
           promote evidence-based practice and incentivize therapeutic innovation
    • Authors: Alice Fortunato; David W. Grainger; Mohamed Abou-El-Enein
      Abstract: Publication date: Available online 31 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Alice Fortunato, David W. Grainger, Mohamed Abou-El-Enein
      Clinical trials are crucial to determining the human safety and efficacy of new therapeutic interventions and innovations. Extraordinary amounts of human experiential data are generated over the course of any clinical drug or therapeutics trial. However, much of these data is never made publicly accessible, either archived openly in accessible formats or venues, published in peer-reviewed journals, or provided to researchers for analysis and scrutiny. Improved, reliable data sharing is essential to inform clinical outcomes and incentivize therapeutic improvements; this need, and the call and concept to improve clinical trial and human therapeutics data accessibility is not new. From patient benefit and value-based medicine perspectives, patient data sharing informs and guides cost savings by eliminating unfruitful therapies, or duplicative trial efforts, also identifying new drug-patient correlations and facilitating improved research strategies. Several recent public and private shifts in clinical data sharing policies and procedures promise to improve access and data utility for patient therapeutic gain. Nonetheless, pharmaceutical industry must at some level protect their commercial interests and avoid misuse of their clinical data. Jeopardizing pharma industry incentives endangers substantial industrial investments in pharmaceutical research and development required for on-going therapeutics innovation. Thus, consistent policies and procedures for sharing human therapeutic performance data that satisfy both clinical data producers and users must become available. Despite some important and impacting recent data sharing developments, further improvements should be considered within the pharmaceutical sector for essential transparency that benefits all stakeholders.
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      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.017
       
  • Extracellular vesicles as modulators of wound healing
    • Authors: Joana Cabral; Aideen E. Ryan; Matthew D. Griffin; Thomas Ritter
      Abstract: Publication date: Available online 31 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Joana Cabral, Aideen E. Ryan, Matthew D. Griffin, Thomas Ritter
      Impaired healing of cutaneous wounds and ulcers continues to have a major impact on the quality of life of millions of people. In recent years, the capacity for stem and progenitor cells to promote wound repair has been investigated with evidence that secreted factors are responsible for the observed therapeutic benefits. This review addresses current evidence in support of stem/progenitor cell-derived extracellular vesicles (EVs) as a regenerative therapy for acceleration of wound healing. Encouraging results for local or systemic administration of EVs have been reported in a range of clinically-relevant animal models of cutaneous wounds. Furthermore, a number of plausible mechanisms involving EV-mediated transfer of proteins and RNAs that trigger pro-repair pathways in target cells have been demonstrated experimentally. However, for successful clinical translation in the coming years, further emphasis on standardized experimental protocols, detailed methodological reporting and clear definition of EV-based therapeutic products will be required.
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      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.018
       
  • Role of MicroRNAs in the pathogenesis and treatment of progressive liver
           injury in NAFLD and liver fibrosis
    • Authors: Qiaozhu Su; Virender Kumar; Neetu Sud; Ram I. Mahato
      Abstract: Publication date: Available online 31 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Qiaozhu Su, Virender Kumar, Neetu Sud, Ram I. Mahato
      Non-alcoholic fatty liver disease (NAFLD) increases the risk of various liver injuries, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis, and ultimately hepatocellular carcinoma (HCC). Ample evidence has suggested that aberrant expression of microRNAs (miRNAs) is functionally involved in the activation of cellular stress, inflammation and fibrogenesis in hepatic cells, including hepatocytes, Kupffer and hepatic stellate cells (HSCs), at different pathological stages of NAFLD and liver fibrosis. Here, we overview recent findings on the potential role of miRNAs in the pathogenesis of NAFLD, including lipotoxicity, oxidative stress, metabolic inflammation and fibrogenesis. We critically assess the literatures on both human subjects and animal models of NAFLD and liver fibrosis with miRNA dysregulation and their mechanisms of actions and liver damage. We further highlight the potential use of miRNA mimics or antimiRNAs as therapeutic approaches for the prevention and treatment of NAFLD and liver fibrosis.
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      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.009
       
  • Polymeric Microneedles for Transdermal Protein Delivery
    • Authors: Yanqi Ye; Jicheng Yu; Di Wen; Anna R. Kahkoska; Zhen Gu
      Abstract: Publication date: Available online 31 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Yanqi Ye, Jicheng Yu, Di Wen, Anna R. Kahkoska, Zhen Gu
      The intrinsic properties of therapeutic proteins present a major impediment for transdermal delivery, including their relatively large molecule size and susceptibility to degradation. One solution is to utilize microneedles (MNs), which are capable of painlessly traversing the stratum corneum and directly translocating protein drugs into the systematic circulation. MNs can be designed to incorporate appropriate structural materials as well as therapeutics or formulations with tailored physicochemical properties. This platform has been applied to deliver drugs both locally and systemically in applications ranging from vaccination to diabetes and cancer therapy. This review surveys the current design and use of polymeric MNs for transdermal protein delivery. The clinical potential and future translation of MNs are also discussed.
      Graphical abstract image

      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.015
       
  • Clinical utility of non-EpCAM based circulating tumor cell assays
    • Authors: R. Garland Austin; Tony Jun Huang; Mengxi Wu; Andrew J. Armstrong; Tian Zhang
      Abstract: Publication date: Available online 31 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): R. Garland Austin, Tony Jun Huang, Mengxi Wu, Andrew J. Armstrong, Tian Zhang
      Methods enabling the isolation, detection, and characterization of circulating tumor cells (CTCs) in blood have clear potential to facilitate precision medicine approaches in patients with cancer, not only for prognostic purposes but also for prediction of the benefits of specific therapies in oncology. However, current CTC assays, which capture CTCs based on expression of epithelial cell adhesion molecule (EpCAM), fail to capture cells from de-differentiated tumors and carcinomas undergoing loss of the epithelial phenotype during the invasion/metastatic process. To address this limitation, many groups are developing non-EpCAM based CTC assays that incorporate nanotechnology to improve test sensitivity for rare but important cells that may otherwise go undetected, and therefore may improve upon clinical utility. In this review, we outline emerging non-EpCAM based CTC assays utilizing nanotechnology approaches for CTC capture or characterization, including dendrimers, magnetic nanoparticles, gold nanoparticles, negative selection chip or software-based on-slide methods, and nano-scale substrates. In addition, we address challenges that remain for the clinical translation of these platforms.
      Graphical abstract image

      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.013
       
  • Improving long-term subcutaneous drug delivery by regulating
           material-bioenvironment interaction
    • Authors: Wei Chen; Bryant C. Yung; Zhiyong Qian; Xiaoyuan Chen
      Abstract: Publication date: Available online 31 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Wei Chen, Bryant C. Yung, Zhiyong Qian, Xiaoyuan Chen
      Subcutaneous long-acting release (LAR) formulations have been extensively developed in the clinic to increase patient compliance and reduce treatment cost. Despite preliminary success for some LAR systems, a major obstacle limiting the therapeutic effect remains on their interaction with surrounding tissues. In this review, we summarize how living bodies respond to injected or implanted materials, and highlight some typical strategies based on smart material design, which may significantly improve long-term subcutaneous drug delivery. Moreover, possible strategies to achieve ultra-long (months, years) subcutaneous drug delivery systems are proposed. Based on these discussions, we believe the well-designed subcutaneous long-acting formulations will hold great promise to improve patient quality of life in the clinic.
      Graphical abstract image

      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.016
       
  • Delivery of cellular factors to regulate bone healing
    • Authors: Alexander Haumer; Paul Emile Bourgine; Paola Occhetta; Gordian Born; Roberta Tasso; Ivan Martin
      Abstract: Publication date: Available online 31 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Alexander Haumer, Paul Emile Bourgine, Paola Occhetta, Gordian Born, Roberta Tasso, Ivan Martin
      Bone tissue has a strong intrinsic regenerative capacity, thanks to a delicate and complex interplay of cellular and molecular processes, which tightly involve the immune system. Pathological settings of anatomical, biomechanical or inflammatory nature may lead to impaired bone healing. Innovative strategies to enhance bone repair, including the delivery of osteoprogenitor cells or of potent cytokines/morphogens, indicate the potential of ‘orthobiologics’, but are not fully satisfactory. Here, we review different approaches based on the delivery of regenerative cues produced by cells but in cell-free, possibly off-the-shelf configurations. Such strategies exploit the paracrine effect of the secretome of mesenchymal stem/stromal cells, presented in soluble form, shuttled through extracellular vesicles, or embedded within the network of extracellular matrix molecules. In addition to osteoinductive molecules, attention is given to factors targeting the resident immune cells, to reshape inflammatory and immunity processes from scarring to regenerative patterns.
      Graphical abstract image

      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.010
       
  • Ocular delivery of proteins and peptides: challenges and novel formulation
           approaches
    • Authors: Abhirup Mandal; Dhananjay Pal; Vibhuti Agrahari; Hoang My Trinh; Mary Joseph; Ashim K. Mitra
      Abstract: Publication date: Available online 13 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Abhirup Mandal, Dhananjay Pal, Vibhuti Agrahari, Hoang My Trinh, Mary Joseph, Ashim K. Mitra
      The impact of proteins and peptides on the treatment of various conditions including ocular diseases over the past few decades has been advanced by substantial breakthroughs in structural biochemistry, genetic engineering, formulation and delivery approaches. Formulation and delivery of proteins and peptides, such as monoclonal antibodies, aptamers, recombinant proteins and peptides to ocular tissues poses significant challenges owing to their large size, poor permeation and susceptibility to degradation. A wide range of advanced drug delivery systems including polymeric controlled release systems, cell-based delivery and nanowafers are being exploited to overcome the challenges of frequent administration to ocular tissues. The next generation systems integrated with new delivery technologies are anticipated to generate improved efficacy and safety through the expansion of the therapeutic target space. This review will highlight recent advances in formulation and delivery strategies of protein and peptide based biopharmaceuticals. We will also describe the current state of proteins and peptides based ocular therapy and future therapeutic opportunities.
      Graphical abstract image

      PubDate: 2018-01-23T01:49:20Z
      DOI: 10.1016/j.addr.2018.01.008
       
  • Addressing barriers to effective cancer immunotherapy with nanotechnology:
           Achievements, challenges, and roadmap to the next generation of
           nanoimmunotherapeutics
    • Authors: Enping Hong; Marina A. Dobrovolskaia
      Abstract: Publication date: Available online 12 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Enping Hong, Marina A. Dobrovolskaia
      Cancer is a complex systemic disorder that affects many organs and tissues and arises from the altered function of multiple cellular and molecular mechanisms. One of the systems malfunctioning in cancer is the immune system. Restoring and improving the ability of the immune system to effectively recognize and eradicate cancer is the main focus of immunotherapy, a topic which has garnered recent and significant interest. The initial excitement about immunotherapy, however, has been challenged by its limited efficacy in certain patient populations and the development of adverse effects such as therapeutic resistance and autoimmunity. At the same time, a number of advances in the field of nanotechnology have sought to address the challenges faced by modern immunotherapeutics and allow these therapeutic strategies to realize their full potential. This endeavour requires an understanding of not only the immunological barriers in cancer but also the mechanisms by which modern technologies and immunotherapeutics modulate the function of the immune system. Herein, we summarize the major barriers relevant to cancer immunotherapy and review current progress in addressing these obstacles using various approaches and clinically approved therapies. We then discuss the remaining challenges and how they can be addressed by nanotechnology. We lay out translational considerations relevant to the therapies described and propose a framework for the development of next-generation nanotechnology-enabled immunotherapies.
      Graphical abstract image

      PubDate: 2018-01-23T01:49:20Z
      DOI: 10.1016/j.addr.2018.01.005
       
  • Microspheres as intraocular therapeutic tools in chronic diseases of the
           optic nerve and retina
    • Authors: Irene Bravo-Osuna; Vanessa Andrés-Guerrero; Alicia Arranz-Romera; Sergio Esteban-Pérez; Irene T. Molina-Martínez; Rocío Herrero-Vanrell
      Abstract: Publication date: Available online 12 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Irene Bravo-Osuna, Vanessa Andrés-Guerrero, Alicia Arranz-Romera, Sergio Esteban-Pérez, Irene T. Molina-Martínez, Rocío Herrero-Vanrell
      Pathologies affecting the optic nerve and the retina are one of the major causes of blindness. These diseases include age-related macular degeneration (AMD), diabetic Retinopathy (DR) and glaucoma, among others. Also, there are genetic disorders that affect the retina causing visual impairment. The prevalence of neurodegenerative diseases of the posterior segment are increased as most of them are related with the elderly. Even with the access to different treatments, there are some challenges in managing patients suffering retinal diseases. One of them is the need for frequent interventions. Also, an unpredictable response to therapy has suggested that different pathways may be playing a role in the development of these diseases. The management of these pathologies requires the development of controlled drug delivery systems able to slow the progression of the disease without the need of frequent invasive interventions, typically related with endophthalmitis, retinal detachment, ocular hypertension, cataract, inflammation, and floaters, among other. Biodegradable microspheres are able to encapsulate low molecular weight substances and large molecules such as biotechnological products. Over the last years, a large variety of active substances has been encapsulated in microspheres with the intention of providing neuroprotection of the optic nerve and the retina. The purpose of the present review is to describe the use of microspheres in chronic neurodegenerative diseases affecting the retina and the optic nerve. The advantage of microencapsulation of low molecular weight drugs as well as therapeutic peptides and proteins to be used as neuroprotective strategy is discussed. Also, a new use of the microspheres in the development of animal models of neurodegeneration of the posterior segment is described.
      Graphical abstract image

      PubDate: 2018-01-23T01:49:20Z
      DOI: 10.1016/j.addr.2018.01.007
       
  • Multifunctional hybrid graphene oxide for circulating tumor cell isolation
           and analysis
    • Authors: Avijit PramaniK; Stacy Jones; Ye Gao; Carrie Sweet; Aruna Vangara; Salma Begum; Paresh Chandra Ray
      Abstract: Publication date: Available online 10 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Avijit PramaniK, Stacy Jones, Ye Gao, Carrie Sweet, Aruna Vangara, Salma Begum, Paresh Chandra Ray
      Even in 21st century, >90% cancer-associated deaths are caused by metastatic disease. Circulating tumor cells (CTCs), which circulate in the blood stream after release from primary tumors, extravasate and form fatal metastases in different organs. Several clinical trials indicate that CTCs can be used as a liquid biopsy of tumors for early diagnosis of cancers. Since CTCs are extremely rare and exhibit heterogeneous biology due to epithelial-mesenchymal transition (EMT), oncologists continue to face enormous challenges in using CTCs as a true “liquid biopsy” for cancer patients. Recent advancements in nanoscience allow us to design nano-architectures with the capability of targeted CTCs isolation and identification. In the current review, we discuss contribution from different groups on the development of graphene oxide based nanoarchitecture for effective isolation and accurate identification of CTCs from whole blood. In the last few years, using zero-dimensional (0D), two dimensional (2D) and three dimensional (3D) multifunctional hybrid graphene oxide (GO), different types of nanoarchitectures have been designed. These nanoarchitectures represent a highly powerful platform for CTC diagnosis. We discuss the major design criteria that have been used to develop hybrid GO nanoarchitectures for selective capture and accurate identification of heterogeneous CTCs from whole blood. At the end, we conclude with the promises, major challenges, and prospect to clinically translate the identification of CTCs using GO based nanotechnology.
      Graphical abstract image

      PubDate: 2018-01-10T12:54:40Z
      DOI: 10.1016/j.addr.2018.01.004
       
  • Size-based separation methods of circulating tumor cells
    • Authors: Si-Jie Hao; Yuan Wan; Yi-Qiu Xia; Xin Zou; Si-Yang Zheng
      Abstract: Publication date: Available online 8 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Si-Jie Hao, Yuan Wan, Yi-Qiu Xia, Xin Zou, Si-Yang Zheng
      Circulating tumor cells (CTCs) originate from the primary tumor mass and enter into the peripheral bloodstream. Compared to other “liquid biopsy” portfolios such as exosome, circulating tumor DNA/RNA (ctDNA/RNA), CTCs have incomparable advantages in analyses of transcriptomics, proteomics, and signal colocalization. Hence, CTCs hold the key to understanding the biology of metastasis and play a vital role in cancer diagnosis, treatment monitoring, and prognosis. Size-based enrichment featureS prominently in CTC isolation. It is a label-free, simple and fast method. Enriched CTCs remain unmodified and viable for a wide range of subsequent analyses. In this review, we comprehensively summarize the differences of size and deformability between CTCs and blood cells, which would facilitate the development of technologies of size-based CTC isolation. Then we review representative size-/deformability-based technologies available for CTC isolation and highlight the recent achievements in molecular analysis of isolated CTCs. To wrap up, we discuss the substantial challenges facing the field, and elaborate on prospects.
      Graphical abstract image

      PubDate: 2018-01-10T12:54:40Z
      DOI: 10.1016/j.addr.2018.01.002
       
  • Molecular analysis of circulating tumors cells: Biomarkers beyond
           enumeration
    • Authors: William L. Hwang; Haley M. Pleskow; David T. Miyamoto
      Abstract: Publication date: Available online 8 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): William L. Hwang, Haley M. Pleskow, David T. Miyamoto
      Advances in our molecular understanding of cancer biology have paved the way to an expanding compendium of molecularly-targeted therapies, accompanied by the urgent need for biomarkers that enable the precise selection of the most appropriate therapies for individual cancer patients. Circulating biomarkers such as circulating tumor cells (CTCs) are poised to fill this need, since they are “liquid biopsies” that can be performed non-invasively and serially, and may capture the spectrum of spatial and temporal tumor heterogeneity better than conventional tissue biopsies. Increasing evidence suggests that moving beyond the enumeration of CTCs towards more sophisticated molecular analyses can provide actionable data that may predict and potentially improve clinical outcomes. In this review, we discuss the potential of molecular CTC analyses to serve as prognostic and predictive biomarkers to guide cancer therapy and early cancer detection. As technologies to capture and analyze CTCs continue to increase in sophistication, we anticipate that the potential clinical applications of CTCs will grow exponentially in the coming years.
      Graphical abstract image

      PubDate: 2018-01-10T12:54:40Z
      DOI: 10.1016/j.addr.2018.01.003
       
  • Co association of mucus modulating agents and nanoparticles for mucosal
           drug delivery
    • Authors: Catherine Taylor Nordgård; Kurt I. Draget
      Abstract: Publication date: Available online 4 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Catherine Taylor Nordgård, Kurt I. Draget
      Nanoparticulate drug delivery systems (nDDS) offer a variety of options when it comes to routes of administration. One possible path is crossing mucosal barriers, such as in the airways and in the GI tract, for systemic distribution or local treatment. The main challenge with this administration route is that the size and surface properties of the nanoparticles, as opposed to small molecular drugs, very often results in mucosal capture, immobilization and removal, which in turn results in a very low bioavailability. Strategies to overcome this challenge do exist, like surface ‘stealth’ modification with PEG. Here we review an alternative or supplemental strategy, co-association of mucus modulating agents with the nDDS to improve bioavailability, where the nDDS may be surface modified or unmodified. This contribution presents some examples on how possible co-association systems may be achieved, using currently marketed mucolytic drugs, alternative formulations or novel agents.
      Graphical abstract image

      PubDate: 2018-01-10T12:54:40Z
      DOI: 10.1016/j.addr.2018.01.001
       
  • Blood derivatives awaken in regenerative medicine strategies to modulate
           wound healing
    • Authors: Bárbara B. Mendes; Manuel Gómez-Florit; Pedro S. Babo; Rui L. Reis; Rui M.A. Domingues; Manuela E. Gomes
      Abstract: Publication date: Available online 28 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Bárbara B. Mendes, Manuel Gómez-Florit, Pedro S. Babo, Rui L. Reis, Rui M.A. Domingues, Manuela E. Gomes
      Blood components play key roles in the modulation of the wound healing process and, together with the provisional fibrin matrix ability to selectively bind bioactive molecules and control its spatial-temporal presentation, define the complex microenvironment that characterize this biological process. As a biomimetic approach, the use of blood derivatives in regenerative strategies has awaken as a source of multiple therapeutic biomolecules. Nevertheless, and despite their clinical relevance, blood derivatives have been showing inconsistent therapeutic results due to several factors, including proper control over their delivery mechanisms. Herein, we highlight recent trends on the use biomaterials to protect, sequester and deliver these pools of biomolecules in tissue engineering and regenerative medicine approaches. Particular emphasis is given to strategies that enable to control their spatiotemporal delivery and improve the selectivity of presentation profiles of the biomolecules derived from blood derivatives rich in platelets. Finally, we discussed possible directions for biomaterials design to potentiate the aimed regenerative effects of blood derivatives and achieve efficient therapies.
      Graphical abstract image

      PubDate: 2018-01-02T19:46:06Z
      DOI: 10.1016/j.addr.2017.12.018
       
  • Advances and new technologies in the treatment of burn injury
    • Authors: Yiwei Wang; Peter K.M. Maitz
      Pages: 1 - 2
      Abstract: Publication date: 1 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 123
      Author(s): Yiwei Wang, Peter K.M. Maitz


      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.11.011
      Issue No: Vol. 123 (2017)
       
  • Burn injury: Challenges and advances in burn wound healing, infection,
           pain and scarring
    • Authors: Yiwei Wang; Joanneke Beekman; Jonathan Hew; Stuart Jackson; Andrea C. Issler-Fisher; Roxanne Parungao; Sepher S. Lajevardi; Zhe Li; Peter K.M. Maitz
      Pages: 3 - 17
      Abstract: Publication date: 1 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 123
      Author(s): Yiwei Wang, Joanneke Beekman, Jonathan Hew, Stuart Jackson, Andrea C. Issler-Fisher, Roxanne Parungao, Sepher S. Lajevardi, Zhe Li, Peter K.M. Maitz
      Severe burn injuries are the most traumatic and physically debilitating injuries affecting nearly every organ system and leading to significant morbidity and mortality. Early burn wound excision and skin grafting are common clinical practices that have significantly improved the outcomes for severe burn injured patients by reducing mortality rate and days of hospital stay. However, slow wound healing, infection, pain, and hypertrophic scarring continue to remain a major challenge in burn research and management. In the present article, we review and discuss issues in the current treatment of burn injuries; the advances and novel strategies developed in the past decade that have improved burn management; and also, pioneer ideas and studies in burn research which aims to enhance burn wound care with a focus on burn wound infection, pain management, treatments for scarring and skin tissue engineering.
      Graphical abstract image

      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.09.018
      Issue No: Vol. 123 (2017)
       
  • Advances in keratinocyte delivery in burn wound care
    • Authors: Britt ter Horst; Gurpreet Chouhan; Naiem S. Moiemen; Liam M. Grover
      Pages: 18 - 32
      Abstract: Publication date: 1 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 123
      Author(s): Britt ter Horst, Gurpreet Chouhan, Naiem S. Moiemen, Liam M. Grover
      This review gives an updated overview on keratinocyte transplantation in burn wounds concentrating on application methods and future therapeutic cell delivery options with a special interest in hydrogels and spray devices for cell delivery. To achieve faster re-epithelialisation of burn wounds, the original autologous keratinocyte culture and transplantation technique was introduced over 3 decades ago. Application types of keratinocytes transplantation have improved from cell sheets to single-cell solutions delivered with a spray system. However, further enhancement of cell culture, cell viability and function in vivo, cell carrier and cell delivery systems remain themes of interest. Hydrogels such as chitosan, alginate, fibrin and collagen are frequently used in burn wound care and have advantageous characteristics as cell carriers. Future approaches of keratinocyte transplantation involve spray devices, but optimisation of application technique and carrier type is necessary.
      Graphical abstract image

      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.06.012
      Issue No: Vol. 123 (2017)
       
  • Nanomedicine and advanced technologies for burns: Preventing infection and
           facilitating wound healing
    • Authors: Mirza Ali Mofazzal Jahromi; Parham Sahandi Zangabad; Seyed Masoud Moosavi Basri; Keyvan Sahandi Zangabad; Ameneh Ghamarypour; Amir R. Aref; Mahdi Karimi; Michael R. Hamblin
      Pages: 33 - 64
      Abstract: Publication date: 1 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 123
      Author(s): Mirza Ali Mofazzal Jahromi, Parham Sahandi Zangabad, Seyed Masoud Moosavi Basri, Keyvan Sahandi Zangabad, Ameneh Ghamarypour, Amir R. Aref, Mahdi Karimi, Michael R. Hamblin
      According to the latest report from the World Health Organization, an estimated 265,000 deaths still occur every year as a direct result of burn injuries. A widespread range of these deaths induced by burn wound happens in low- and middle-income countries, where survivors face a lifetime of morbidity. Most of the deaths occur due to infections when a high percentage of the external regions of the body area is affected. Microbial nutrient availability, skin barrier disruption, and vascular supply destruction in burn injuries as well as systemic immunosuppression are important parameters that cause burns to be susceptible to infections. Topical antimicrobials and dressings are generally employed to inhibit burn infections followed by a burn wound therapy, because systemic antibiotics have problems in reaching the infected site, coupled with increasing microbial drug resistance. Nanotechnology has provided a range of molecular designed nanostructures (NS) that can be used in both therapeutic and diagnostic applications in burns. These NSs can be divided into organic and non-organic (such as polymeric nanoparticles (NPs) and silver NPs, respectively), and many have been designed to display multifunctional activity. The present review covers the physiology of skin, burn classification, burn wound pathogenesis, animal models of burn wound infection, and various topical therapeutic approaches designed to combat infection and stimulate healing. These include biological based approaches (e.g. immune-based antimicrobial molecules, therapeutic microorganisms, antimicrobial agents, etc.), antimicrobial photo- and ultrasound-therapy, as well as nanotechnology-based wound healing approaches as a revolutionizing area. Thus, we focus on organic and non-organic NSs designed to deliver growth factors to burned skin, and scaffolds, dressings, etc. for exogenous stem cells to aid skin regeneration. Eventually, recent breakthroughs and technologies with substantial potentials in tissue regeneration and skin wound therapy (that are as the basis of burn wound therapies) are briefly taken into consideration including 3D-printing, cell-imprinted substrates, nano-architectured surfaces, and novel gene-editing tools such as CRISPR-Cas.
      Graphical abstract image

      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.08.001
      Issue No: Vol. 123 (2017)
       
  • The effects of major burn related pathophysiological changes on the
           pharmacokinetics and pharmacodynamics of drug use: An appraisal utilizing
           antibiotics
    • Authors: Andrew A. Udy; Jason A. Roberts; Jeffrey Lipman; Stijn Blot
      Pages: 65 - 74
      Abstract: Publication date: 1 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 123
      Author(s): Andrew A. Udy, Jason A. Roberts, Jeffrey Lipman, Stijn Blot
      Patients suffering major burn injury represent a unique population of critically ill patients. Widespread skin and tissue damage causes release of systemic inflammatory mediators that promote endothelial leak, extravascular fluid shifts, and cardiovascular derangement. This phase is characterized by relative intra-vascular hypovolaemia and poor peripheral perfusion. Large volume intravenous fluid resuscitation is generally required. The patients' clinical course is then typically complicated by ongoing inflammation, protein catabolism, and marked haemodynamic perturbation. At all times, drug distribution, metabolism, and elimination are grossly distorted. For hydrophilic agents, changes in volume of distribution and clearance are marked, resulting in potentially sub-optimal drug exposure. In the case of antibiotics, this may then promote treatment failure, or the development of bacterial drug resistance. As such, empirical dose selection and pharmaceutical development must consider these features, with the application of strategies that attempt to counter the unique pharmacokinetic changes encountered in this setting.
      Graphical abstract image

      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.09.019
      Issue No: Vol. 123 (2017)
       
  • Scar management in burn injuries using drug delivery and molecular
           signaling: Current treatments and future directions
    • Authors: Saeid Amini-Nik; Yusef Yousuf; Marc G. Jeschke
      Pages: 135 - 154
      Abstract: Publication date: 1 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 123
      Author(s): Saeid Amini-Nik, Yusef Yousuf, Marc G. Jeschke
      In recent decades, there have been tremendous improvements in burn care that have allowed patients to survive severe burn injuries that were once fatal. However, a major limitation of burn care currently is the development of hypertrophic scars in approximately 70% of patients. This significantly decreases the quality of life for patients due to the physical and psychosocial symptoms associated with scarring. Current approaches to manage scarring include surgical techniques and non-surgical methods such as laser therapy, steroid injections, and compression therapy. These treatments are limited in their effectiveness and regularly fail to manage symptoms. As a result, the development of novel treatments that aim to improve outcomes and quality of life is imperative. Drug delivery that targets the molecular cascades of wound healing to attenuate or prevent hypertrophic scarring is a promising approach that has therapeutic potential. In this review, we discuss current treatments for scar management after burn injury, and how drug delivery targeting molecular signaling can lead to new therapeutic strategies.
      Graphical abstract image

      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.07.017
      Issue No: Vol. 123 (2017)
       
  • Editorial board members
    • Abstract: Publication date: 1 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 123


      PubDate: 2017-12-23T19:45:52Z
       
  • Efficacy and safety concerns over the use of mucus modulating agents for
           drug delivery using nanoscale systems
    • Authors: Peter I. Chater; Matthew D. Wilcox; Jeffrey P. Pearson
      Abstract: Publication date: Available online 13 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Peter I. Chater, Matthew D. Wilcox, Jeffrey P. Pearson
      Drug delivery to the mucus covered mucosae is fraught with difficulties and many different approaches have been developed to permeate the mucus barrier. Generally by modifying the delivery system to avoid interaction with the mucus. These modifications are reviewed here in terms of efficacy and safety. These are particular problems for oral delivery the pharmaceutical industry's favoured route for drug administration. For effective delivery through the gastrointestinal tract a drug must pass through three barriers in sufficient amounts to yield a biological effect. These barriers are the digestive barrier in the lumen, the mucus barrier, and the epithelial barrier. Other approaches involve mucolytic agents added with or prior to the delivery system or agents regulating mucus production and are reviewed here. In terms of safety, a key property of a mucus modulating delivery system is that it must not damage the protective function of the mucus layer.
      Graphical abstract image

      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.12.006
       
  • Technological strategies to estimate and control diffusive passage times
           through the mucus barrier in mucosal drug delivery
    • Authors: Jay M. Newby; Ian Seim; Martin Lysy; Yun Ling; Justin Huckaby; Samuel K. Lai; M. Gregory Forest
      Abstract: Publication date: Available online 12 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Jay M. Newby, Ian Seim, Martin Lysy, Yun Ling, Justin Huckaby, Samuel K. Lai, M. Gregory Forest
      In mucosal drug delivery, two design goals are desirable: 1) insure drug passage through the mucosal barrier to the epithelium prior to drug removal from the respective organ via mucus clearance; and 2) design carrier particles to achieve a prescribed arrival time and drug uptake schedule at the epithelium. Both goals are achievable if one can control “one-sided” diffusive passage times of drug carrier particles: from deposition at the mucus interface, through the mucosal barrier, to the epithelium. The passage time distribution must be, with high confidence, shorter than the timescales of mucus clearance to maximize drug uptake. For 100nm and smaller drug-loaded nanoparticulates, as well as pure drug powders or drug solutions, diffusion is normal (i.e., Brownian) and rapid, easily passing through the mucosal barrier prior to clearance. Major challenges in quantitative control over mucosal drug delivery lie with larger drug-loaded nanoparticulates that are comparable to or larger than the pores within the mucus gel network, for which diffusion is not simple Brownian motion and typically much less rapid; in these scenarios, a timescale competition ensues between particle passage through the mucus barrier and mucus clearance from the organ. In the lung, as a primary example, coordinated cilia and air drag continuously transport mucus toward the trachea, where mucus and trapped cargo are swallowed into the digestive tract. Mucus clearance times in lung airways range from minutes to hours or significantly longer depending on deposition in the upper, middle, lower airways and on lung health, giving a wide time window for drug-loaded particle design to achieve controlled delivery to the epithelium. We review the physical and chemical factors (of both particles and mucus) that dictate particle diffusion in mucus, and the technological strategies (theoretical and experimental) required to achieve the design goals. First we describe an idealized scenario — a homogeneous viscous fluid of uniform depth with a particle undergoing passive normal diffusion — where the theory of Brownian motion affords the ability to rigorously specify particle size distributions to meet a prescribed, one-sided, diffusive passage time distribution. Furthermore, we describe how the theory of Brownian motion provides the scaling of one-sided diffusive passage times with respect to mucus viscosity and layer depth, and under reasonable caveats, one can also prescribe passage time scaling due to heterogeneity in viscosity and layer depth. Small-molecule drugs and muco-inert, drug-loaded carrier particles 100nm and smaller fall into this class of rigorously controllable passage times for drug delivery. Second we describe the prevalent scenarios in which drug-loaded carrier particles in mucus violate simple Brownian motion, instead exhibiting anomalous sub-diffusion, for which all theoretical control over diffusive passage times is lost, and experiments are prohibitive if not impossible to measure one-sided passage times. We then discuss strategies to overcome these roadblocks, requiring new particle-tracking experiments and emerging advances in theory and computation of anomalous, sub-diffusive processes that are necessary to predict and control one-sided particle passage times from deposition at the mucosal interface to epithelial uptake. We highlight progress to date, remaining hurdles, and prospects for achieving the two design goals for 200nm and larger, drug-loaded, non-dissolving, nanoparticulates.
      Graphical abstract image

      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.12.002
       
  • Animal Models of Smoke Inhalation Injury and Related Acute and Chronic
           Lung Diseases
    • Authors: Katarzyna Reczyńska; Priyanka Tharkar; Sally Yunsun Kim; Yiwei Wang; Elzbieta Pamuła; Hak-Kim Chan; Wojciech Chrzanowski
      Abstract: Publication date: Available online 3 November 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Katarzyna Reczyńska, Priyanka Tharkar, Sally Yunsun Kim, Yiwei Wang, Elzbieta Pamuła, Hak-Kim Chan, Wojciech Chrzanowski
      Smoke inhalation injury leads to various acute and chronic lung diseases and thus is the dominant cause of fire-related fatalities. In a search for an effective treatment and validation of therapies different classes of animal models have been developed, which include both small and large animals. These models have advanced our understanding of the mechanism of smoke inhalation injury, enabling a better understanding of pathogenesis and pathophysiology and development of new therapies. However, none of the animal models fully mirrors human lungs and their pathologies. All animal models have their limitations in replicating complex clinical conditions associated with smoke inhalation injury in humans. Therefore, for a correct interpretation of the results and to avoid bias, a precise understanding of similarities and differences of lungs between different animal species and humans is critical. We have reviewed and presented comprehensive comparison of different animal models and their clinical relevance. We presented an overview of methods utilized to induce smoke inhalation injuries, airway micro−/ macrostructure, advantages and disadvantages of the most commonly used small and large animal models.
      Graphical abstract image

      PubDate: 2017-11-09T00:59:41Z
      DOI: 10.1016/j.addr.2017.10.005
       
  • Stem Cells, Niches and Scaffolds: Applications to Burns and Wound Care
    • Authors: Suzanne M. Watt; Jonathan M. Pleat
      Abstract: Publication date: Available online 26 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Suzanne M. Watt, Jonathan M. Pleat
      The importance of skin to survival, and the devastating physical and psychological consequences of scarring following reparative healing of extensive or difficult to heal human wounds, cannot be disputed. We discuss the significant challenges faced by patients and healthcare providers alike in treating these wounds. New state of the art technologies have provided remarkable insights into the role of skin stem and progenitor cells and their niches in maintaining skin homeostasis and in reparative wound healing. Based on this knowledge, we examine different approaches to repair extensive burn injury and chronic wounds, including full and split thickness skin grafts, temporising matrices and scaffolds and composite cultured skin products. Notable developments include next generation skin substitutes to replace split thickness skin autografts and next generation gene editing coupled with cell therapies to treat genodermatoses. Further refinements are predicted with the advent of bioprinting technologies, and newly defined biomaterials and autologous cell sources that can be engineered to more accurately replicate human skin architecture, function and cosmesis. These advances will undoubtedly improve quality of life for patients with extensive burns and difficult to heal wounds.
      Graphical abstract image

      PubDate: 2017-11-02T00:40:33Z
      DOI: 10.1016/j.addr.2017.10.012
       
  • Restoration of skin pigmentation after deep partial or full-thickness burn
           injury
    • Authors: Niann-Tzyy Dai; Hsin-I Chang; Yi-Wen Wang; Keng-Yen Fu; Tai-Chun Huang; Nien-Chi Huang; Jhen-Kai Li; Pai-Shan Hsieh; Lien-Guo Dai; Chao-Kuei Hsu; Peter K. Maitz
      Abstract: Publication date: Available online 24 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Niann-Tzyy Dai, Hsin-I Chang, Yi-Wen Wang, Keng-Yen Fu, Tai-Chun Huang, Nien-Chi Huang, Jhen-Kai Li, Pai-Shan Hsieh, Lien-Guo Dai, Chao-Kuei Hsu, Peter K. Maitz
      Significant skin pigmentation changes occur when patients suffer deep burn injuries. These pigmentation disorders may cause not only cosmetic and psychological issues, but more importantly it increases the risk of skin cancer or photoaging. Severe burns significantly effect on the process of repigmentation as the pigmentation is tightly regulated by cell proliferation and differentiation of melanocytes and melanocyte stem cells which are housing in the epidermis and hair follicles of the skin. In the present review, we discuss the possible mechanisms to replenish the melanocytes from the healthy epidermis and hair follicles surrounding burn wounds. The molecular mechanisms of skin repigmentation following healing of burn injuries includes the differentiation of melanoblasts into melanocytes, the distribution and responses of melanocytes and melanocyte stem cells after burn injury, and the regulation of melanin production. We also reviewed advanced therapeutic strategies to treat pigmentation disorders, such as convectional surgery, laser, UV treatment and emerging concepts in skin tissue-engineering.
      Graphical abstract image

      PubDate: 2017-10-26T01:44:14Z
      DOI: 10.1016/j.addr.2017.10.010
       
  • The application of mesenchymal stem cells to treat thermal and radiation
           burns
    • Authors: Kathleen Rodgers; Sachin S. Jadhav
      Abstract: Publication date: Available online 12 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Kathleen Rodgers, Sachin S. Jadhav
      Mesenchymal stem cells (MSCs) have been developed for a number of indications due to their regenerative and anti-inflammatory phenotypes and their utility is enhanced by the fact that allogeneic transplant is feasible with this cell type. Animal studies and early human cases indicate that this has the potential to be an exciting new therapy for treating chronic non-healing wounds such as diabetic ulcers, burns and cutaneous radiation burns. This review will focus on the use of MSCs to treat thermal and radiation burns. Large, severe burns are difficult to treat and pose a major public health burden worldwide. They are characterized by an extensive loss of the outer protective barrier, delayed wound healing, increased oxidative stress and a heightened inflammatory state. The breakdown of the protective barrier results in increased susceptibility to fluid loss and bacterial sepsis. In the case of radiation burns, chronic inflammation can result in subsequent waves of tissue injury leading to skin breakdown and necrosis. The aim of this review is to summarize the current knowledge on MSCs in treating thermal and radiation burns along with the specific scope of characterizing the biologic function of MSCs that help enhance wound healing in these chronic injuries.
      Graphical abstract image

      PubDate: 2017-10-18T00:26:56Z
      DOI: 10.1016/j.addr.2017.10.003
       
 
 
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