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  [3175 journals]
  • Perspectives on the past, present, and future of cancer nanomedicine
    • Authors: Yu Seok Youn; You Han Bae
      Abstract: Publication date: Available online 18 May 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Yu Seok Youn, You Han Bae
      The justification of cancer nanomedicine relies on enhanced permeation (EP) and retention (R) effect and the capability of intracellular targeting due primarily to size after internalization (endocytosis) into the individual target cells. The EPR effect implies improved efficacy. Affinity targeting for solid tumors only occur after delivery to individual cells, which help internalization and/or retention. The design principles have been supported by animal results in numerous publications, but hardly translated. The natures of EP and R, such as frequency of large openings in tumor vasculature and their dynamics, are not understood, in particular, in clinical settings. Although various attempts to address the issues related to EP and delivery, by modifying design factors and manipulating tumor microenvironment, are being reported, they are still verified in artificial rodent tumors which do not mimic the nature of human tumor physiology/pathology in terms of transport and delivery. The clinical trials of experimental nanomedicine have experienced unexpected adverse effects with modest improvement in efficacy when compared to current frontline therapy. Future nanomedicine may require new design principles without consideration of EP and affinity targeting. A possible direction is to set new approaches to intentionally minimize adverse effects, rather than aiming at better efficacy, which can widen the therapeutic window of an anticancer drug of interest. Broadening indications and administration routes of developed therapeutic nanotechnology would benefit patients.
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      PubDate: 2018-05-18T10:57:57Z
      DOI: 10.1016/j.addr.2018.05.008
       
  • Stem cell-based retina models
    • Authors: Kevin Achberger; Jasmin C. Haderspeck; Alexander Kleger; Stefan Liebau
      Abstract: Publication date: Available online 17 May 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Kevin Achberger, Jasmin C. Haderspeck, Alexander Kleger, Stefan Liebau
      From the early days of cell biological research, the eye—especially the retina—has evoked broad interest among scientists. The retina has since been thoroughly investigated and numerous models have been exploited to shed light on its development, morphology, and function. Apart from various animal models and human clinical and anatomical research, stem cell-based models of animal and human cells of origin have entered the field, especially during the last decade. Despite the observation that the retina of different species comprises endogenous stem cells, most stem cell-related research in the human retina is now based on pluripotent stem cell models. Herein, systems of two-dimensional (2D) cultures and co-cultures of distinctly differentiated retinal subtypes revealed a variety of cellular aspects but have in many aspects been replaced by three-dimensional (3D) structures—the so-called retinal organoids. These organoids not only contain all major retinal cell subtypes compared to the physiological situation, but also show a distinct layering in close proximity to the in vivo morphology. Nevertheless, all these models have inherent advantages and disadvantages, which are expounded and summarized in this review. Finally, we discuss current application aspects of stem cell-based retina models and the specific promises they hold for the future.
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      PubDate: 2018-05-17T10:57:12Z
      DOI: 10.1016/j.addr.2018.05.005
       
  • Production of pure drug nanocrystals and Nano Co-crystals by confinement
           methods
    • Authors: Flavia Fontana; Patricia Figueiredo; Pei Zhang; Jouni T. Hirvonen; Dongfei Liu; Helder A. Santos
      Abstract: Publication date: Available online 5 May 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Flavia Fontana, Patricia Figueiredo, Pei Zhang, Jouni T. Hirvonen, Dongfei Liu, Helder A. Santos
      The use of drug nanocrystals in the drug formulation is increasing due to the large number of poorly water-soluble drug compounds synthetized and due to the advantages brought by the nanonization process. The downsizing processes are done using a top-down approach (milling and homogenization currently employed at the industrial level), while the crystallization process is performed by bottom-up techniques (e.g., antisolvent precipitation to the use of supercritical fluids or spray and freeze drying). In addition, the production of nanocrystals in confined environment can be achieved within microfluidics channels. This review analyzes the processes for the preparation of nanocrystals and co-crystals, divided by top-down and bottom-up approaches, together with their combinations. The combination of both strategies merges the favorable features of each process and avoids the disadvantages of single processes. Overall, the applicability of drug nanocrystals is highlighted by the widespread research on the production processes at the engineering, pharmaceutical, and nanotechnology level.
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      PubDate: 2018-05-17T10:57:12Z
      DOI: 10.1016/j.addr.2018.05.002
       
  • Electrospinning: An enabling nanotechnology platform for drug delivery and
           regenerative medicine
    • Authors: Shixuan Chen; Ruiquan Li; Xiaoran Li; Jingwei Xie
      Abstract: Publication date: Available online 2 May 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Shixuan Chen, Ruiquan Li, Xiaoran Li, Jingwei Xie
      Electrospinning provides an enabling nanotechnology platform for generating a rich variety of novel structured materials in many biomedical applications including drug delivery, biosensing, tissue engineering, and regenerative medicine. In this review article, we begin with a thorough discussion on the method of producing 1D, 2D, and 3D electrospun nanofiber materials. In particular, we emphasize on how the 3D printing technology can contribute to the improvement of traditional electrospinning technology for the fabrication of 3D electrospun nanofiber materials as drug delivery devices/implants, scaffolds or living tissue constructs. We then highlight several notable examples of electrospun nanofiber materials in specific biomedical applications including cancer therapy, guiding cellular responses, engineering in vitro 3D tissue models, and tissue regeneration. Finally, we finish with conclusions and future perspectives of electrospun nanofiber materials for drug delivery and regenerative medicine.
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      PubDate: 2018-05-17T10:57:12Z
      DOI: 10.1016/j.addr.2018.05.001
       
  • Cell encapsulation: Overcoming barriers in cell transplantation in
           diabetes and beyond
    • Authors: Marco Farina; Jenolyn F. Alexander; Usha Thekkedath; Mauro Ferrari; Alessandro Grattoni
      Abstract: Publication date: Available online 30 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Marco Farina, Jenolyn F. Alexander, Usha Thekkedath, Mauro Ferrari, Alessandro Grattoni
      Cell-based therapy is emerging as a promising strategy for treating a wide range of human diseases, such as diabetes, blood disorders, acute liver failure, spinal cord injury, and several types of cancer. Pancreatic islets, blood cells, hepatocytes, and stem cells are among the many cell types currently used for this strategy. The encapsulation of these “therapeutic” cells is under intense investigation to not only prevent immune rejection but also provide a controlled and supportive environment so they can function effectively. Some of the advanced encapsulation systems provide active agents to the cells and enable a complete retrieval of the graft in the case of an adverse body reaction. Here, we review various encapsulation strategies developed in academic and industrial settings, including the state-of-the-art technologies in advanced preclinical phases as well as those undergoing clinical trials, and assess their advantages and challenges. We also emphasize the importance of stimulus-responsive encapsulated cell systems that provide a “smart and live” therapeutic delivery to overcome barriers in cell transplantation as well as their use in patients.
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      PubDate: 2018-05-01T20:07:30Z
      DOI: 10.1016/j.addr.2018.04.018
       
  • Fibrillin microfibrils and proteases, key integrators of fibrotic pathways
    • Authors: Paola Zigrino; Gerhard Sengle
      Abstract: Publication date: Available online 27 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Paola Zigrino, Gerhard Sengle
      Supramolecular networks composed of multi-domain ECM proteins represent intricate cellular microenvironments which are required to balance tissue homeostasis and direct remodeling. Structural deficiency in ECM proteins results in imbalances in ECM-cell communication resulting often times in fibrotic reactions. To understand how individual components of the ECM integrate communication with the cell surface by presenting growth factors or providing fine-tuned biomechanical properties is mandatory for gaining a better understanding of disease mechanisms in the quest for new therapeutic approaches. Here we provide an overview about what we can learn from inherited connective tissue disorders caused primarily by mutations in fibrillin-1 and binding partners as well as by altered ECM processing leading to defined structural changes and similar functional knock-in mouse models. We will utilize this knowledge to propose new molecular hypotheses which should be tested in future studies.
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      PubDate: 2018-05-01T20:07:30Z
      DOI: 10.1016/j.addr.2018.04.019
       
  • Intervertebral disc regeneration: From cell therapy to the development of
           novel bioinspired endogenous repair strategies
    • Authors: Johann Clouet; Marion Fusellier; Anne Camus; Catherine Le Visage; Jérôme Guicheux
      Abstract: Publication date: Available online 26 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Johann Clouet, Marion Fusellier, Anne Camus, Catherine Le Visage, Jérôme Guicheux
      Low back pain (LBP), frequently associated with intervertebral disc (IVD) degeneration, is a major public health concern. LBP is currently managed by pharmacological treatments and, if unsuccessful, by invasive surgical procedures, which do not counteract the degenerative process. Considering that IVD cell depletion is critical in the degenerative process, the supplementation of IVD with reparative cells, associated or not with biomaterials, has been contemplated. Recently, the discovery of reparative stem/progenitor cells in the IVD has led to increased interest in the potential of endogenous repair strategies. Recruitment of these cells by specific signals might constitute an alternative strategy to cell transplantation. Here, we review the status of cell-based therapies for treating IVD degeneration and emphasize the current concept of endogenous repair as well as future perspectives. This review also highlights the challenges of the mobilization/differentiation of reparative progenitor cells through the delivery of biologics factors to stimulate IVD regeneration.
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      PubDate: 2018-05-01T20:07:30Z
      DOI: 10.1016/j.addr.2018.04.017
       
  • Sphingolipids as targets for inhalation treatment of cystic fibrosis
    • Authors: Katrin Anne Becker; Joachim Riethmüller; Aaron P. Seitz; Aaron Gardner; Ryan Boudreau; Markus Kamler; Burkhard Kleuser; Edward Schuchman; Charles C. Caldwell; Michael J. Edwards; Heike Grassmé; Malcolm Brodlie; Erich Gulbins
      Abstract: Publication date: Available online 24 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Katrin Anne Becker, Joachim Riethmüller, Aaron P. Seitz, Aaron Gardner, Ryan Boudreau, Markus Kamler, Burkhard Kleuser, Edward Schuchman, Charles C. Caldwell, Michael J. Edwards, Heike Grassmé, Malcolm Brodlie, Erich Gulbins
      Studies over the past several years have demonstrated the important role of sphingolipids in cystic fibrosis (CF), chronic obstructive pulmonary disease and acute lung injury. Ceramide is increased in airway epithelial cells and alveolar macrophages of CF mice and humans, while sphingosine is dramatically decreased. This increase in ceramide results in chronic inflammation, increased death of epithelial cells, release of DNA into the bronchial lumen and thereby an impairment of mucociliary clearance; while the lack of sphingosine in airway epithelial cells causes high infection susceptibility in CF mice and possibly patients. The increase in ceramide mediates an ectopic expression of β1-integrins in the luminal membrane of CF epithelial cells, which results, via an unknown mechanism, in a down-regulation of acid ceramidase. It is predominantly this down-regulation of acid ceramidase that results in the imbalance of ceramide and sphingosine in CF cells. Correction of ceramide and sphingosine levels can be achieved by inhalation of functional acid sphingomyelinase inhibitors, recombinant acid ceramidase or by normalization of β1-integrin expression and subsequent re-expression of endogenous acid ceramidase. These treatments correct pulmonary inflammation and prevent or treat, respectively, acute and chronic pulmonary infections in CF mice with Staphylococcus aureus and mucoid or non-mucoid Pseudomonas aeruginosa. Inhalation of sphingosine corrects sphingosine levels only and seems to mainly act against the infection. Many antidepressants are functional inhibitors of the acid sphingomyelinase and were designed for systemic treatment of major depression. These drugs could be repurposed to treat CF by inhalation.
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      PubDate: 2018-04-25T11:32:05Z
      DOI: 10.1016/j.addr.2018.04.015
       
  • Mechanistical retinal drug targets and challenges
    • Authors: Kai Kaarniranta; Heping Xu; Anu Kauppinen
      Abstract: Publication date: Available online 23 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Kai Kaarniranta, Heping Xu, Anu Kauppinen
      The retina is constantly exposed to light that increases reactive oxygen species in retina. Oxidative stress, inflammation and neurodegeneration are the major contributors in the most common retinal diseases, such as age-related macular degeneration (AMD), glaucoma and diabetic retinopathy (DR). Emerging developments and research for novel therapy targets and drug delivery to the posterior segment offer a promising future for the treatment of retinal diseases including rare hereditary diseases. In this review we discuss about promising mechanistical retinal drug targets. Vascular endothelial growth factor (VEGF) signaling and anti-VEGF treatments are excluded.
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      PubDate: 2018-04-25T11:32:05Z
      DOI: 10.1016/j.addr.2018.04.016
       
  • Regulatory pitfalls and opportunities when repurposing for inhalation
           therapy
    • Authors: Svetlana Lyapustina
      Abstract: Publication date: Available online 19 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Svetlana Lyapustina
      This article reviews regulatory considerations for companies wishing to develop drugs for delivery via the respiratory tract (e.g., by oral inhalation or intranasally) using molecules previously approved for a different therapeutic indication and/or a different delivery route. Conceptually, such repurposing has many medical and business advantages, but turning promising ideas into real products requires overcoming a number of practical challenges. Obtaining regulatory approval to market a candidate product comes at the end of a product development, but being aware of the regulatory requirements is necessary before the development even starts. Understanding the scope and type of data that regulatory agencies would like to see may have a decisive influence on the design of the development program itself. For example, even for repurposed drugs, safety, efficacy, quality, and usability must be demonstrated, either from prior knowledge or through newly generated data. Furthermore, products for respiratory delivery have unique regulatory challenges due to the nature of these drug-device combinations.
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      PubDate: 2018-04-25T11:32:05Z
      DOI: 10.1016/j.addr.2018.04.013
       
  • Impact of aging, Alzheimer's disease and Parkinson's disease on the
           blood-brain barrier transport of therapeutics
    • Authors: Yijun Pan; Joseph A. Nicolazzo
      Abstract: Publication date: Available online 14 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Yijun Pan, Joseph A. Nicolazzo
      Older people are at greater risk of medicine-induced toxicities resulting from either increased drug sensitivity or age-related pharmacokinetic changes. The scenario is further complicated with the two most prevalent age-related neurodegenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD). With aging, AD and PD, there is growing evidence of altered structure and function of the blood-brain barrier (BBB), including modifications to tight junctions and efflux transporters, such as P-glycoprotein. The subsequent impact on CNS drug exposure and risk of neurotoxicity from systemically-acting medicines is less well characterized. The purpose of this review, therefore, is to provide an overview of the multiple changes that occur to the BBB as a result of aging, AD and PD, and the impact that such changes have on CNS exposure of drugs, based on studies conducted in aged rodents or rodent models of disease, and in elderly people with and without AD or PD.
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      PubDate: 2018-04-15T09:22:44Z
      DOI: 10.1016/j.addr.2018.04.009
       
  • Dosage form modification and oral drug delivery in older people
    • Authors: Esther T.L. Lau; Kathryn J. Steadman; Julie A.Y. Cichero; Lisa M. Nissen
      Abstract: Publication date: Available online 13 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Esther T.L. Lau, Kathryn J. Steadman, Julie A.Y. Cichero, Lisa M. Nissen
      Many people cannot swallow whole tablets and capsules. The cause ranges from difficulties overriding the natural instinct to chew solids/foodstuff before swallowing, to a complex disorder of swallowing function affecting the ability to manage all food and fluid intake. Older people can experience swallowing difficulties because of co-morbidities, age-related physiological changes, and polypharmacy. To make medicines easier to swallow, many people will modify the medication dosage form e.g. split or crush tablets, and open capsules. Some of the challenges associated with administering medicines to older people, and issues with dosage form modification will be reviewed. Novel dosage forms in development are promising and may help overcome some of the issues. However, until these are more readily available, effective interdisciplinary teams, and improving patient health literacy will help reduce the risk of medication misadventures in older people.
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      PubDate: 2018-04-15T09:22:44Z
      DOI: 10.1016/j.addr.2018.04.012
       
  • Scarless wound healing: From development to senescence
    • Authors: Harris Pratsinis; Eleni Mavrogonatou; Dimitris Kletsas
      Abstract: Publication date: Available online 12 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Harris Pratsinis, Eleni Mavrogonatou, Dimitris Kletsas
      An essential element of tissue homeostasis is the response to injuries, cutaneous wound healing being the most studied example. In the adults, wound healing aims at quickly restoring the barrier function of the skin, leading however to scar, a dysfunctional fibrotic tissue. On the other hand, in fetuses a scarless tissue regeneration takes place. During ageing, the wound healing capacity declines; however, in the absence of comorbidities a higher quality in tissue repair is observed. Senescent cells have been found to accumulate in chronic unhealed wounds, but more recent reports indicate that their transient presence may be beneficial for tissue repair. In this review data on skin wound healing and scarring are presented, covering the whole spectrum from early embryonic development to adulthood, and furthermore until ageing of the organism.
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      PubDate: 2018-04-15T09:22:44Z
      DOI: 10.1016/j.addr.2018.04.011
       
  • Delivering drugs to the lungs: The history of repurposing in the treatment
           of respiratory diseases
    • Authors: Stephen P. Newman
      Abstract: Publication date: Available online 11 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Stephen P. Newman
      The repurposing of drug delivery by the pulmonary route has been applied to treatment and prophylaxis of an increasingly wide range of respiratory diseases. Repurposing has been most successful for the delivery of inhaled bronchodilators and corticosteroids in patients with asthma and chronic obstructive pulmonary disease (COPD). Repurposing utilizes the advantages that the pulmonary route offers in terms of more targeted delivery to the site of action, the use of smaller doses, and a lower incidence of side-effects. Success has been more variable for other drugs and treatment indications. Pulmonary delivery is now well established for delivery of inhaled antibiotics in cystic fibrosis (CF), and in the treatment of pulmonary arterial hypertension (PAH). Other inhaled treatments such as those for idiopathic pulmonary fibrosis (IPF), lung transplant rejection or tuberculosis may also become routine. Repurposing has progressed in parallel with the development of new drugs, inhaler devices and formulations.
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      PubDate: 2018-04-15T09:22:44Z
      DOI: 10.1016/j.addr.2018.04.010
       
  • Aptamers as targeting ligands and therapeutic molecules for overcoming
           drug resistance in cancers
    • Authors: Gang Zhou; Olivier Latchoumanin; Lionel Hebbard; Wei Duan; Christopher Liddle; Jacob George; Liang Qiao
      Abstract: Publication date: Available online 6 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Gang Zhou, Olivier Latchoumanin, Lionel Hebbard, Wei Duan, Christopher Liddle, Jacob George, Liang Qiao
      Traditional anticancer therapies are often unable to completely eradicate the tumor bulk due to multi-drug resistance (MDR) of cancers. A number of mechanisms such as micro-environmental stress and overexpression of drug efflux pumps are involved in the MDR process. Hence, therapeutic strategies for overcoming MDR are urgently needed to improve cancer treatment efficacy. Aptamers are short single-stranded oligonucleotides or peptides exhibiting unique three-dimensional structures and possess several unique advantages over conventional antibodies such as low immunogenicity and stronger tissue-penetration capacity. Aptamers targeting cancer-associated receptors have been explored to selectively deliver a therapeutic cargo (anticancer drugs, siRNAs, miRNAs and drug-carriers) to the intratumoral compartment where they can exert better tumor-killing effects. In this review, we summarize current knowledge of the multiple regulatory mechanisms of MDR, with a particular emphasis on aptamer-mediated novel therapeutic agents and strategies that seek to reversing MDR. The challenges associated with aptamer-based agents and approaches are also discussed.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.04.005
       
  • Nucleic acids delivering nucleic acids
    • Authors: Silvia Catuogno; Carla Lucia Esposito; Gerolama Condorelli; Vittorio de Franciscis
      Abstract: Publication date: Available online 6 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Silvia Catuogno, Carla Lucia Esposito, Gerolama Condorelli, Vittorio de Franciscis
      Nucleic acid therapeutics, including siRNAs, miRNAs/antimiRs, gRNAs and ASO, represent innovative and highly promising molecules for the safe treatment of a wide range of pathologies. The efficiency of systemic treatments is impeded by 1) the need to overcome physical and functional barriers in the organism, and 2) to accumulate in the intracellular active site at therapeutic concentrations. Although oligonucleotides either as modified naked molecules or complexed with delivery carriers have revealed to be effectively delivered to the affected target cells, this is restricted to topic treatments or to a few highly vascularized tissues. Therefore, the development of effective strategies for therapeutic nucleic acid selective delivery to target tissues is of primary importance in order to reduce the occurrence of undesired effects on non-target healthy tissues and to permit their translation to clinic. Due to their high affinity for specific ligands, high tissue penetration and chemical flexibility, short single-stranded nucleic acid aptamers are emerging as very attractive carriers for various therapeutic oligonucleotides. Yet, different aptamer-based bioconjugates, able to provide accumulation into target tissues, as well as efficient processing of therapeutic oligonucleotides, have been developed. In this respect, nucleic acid aptamer-mediated delivery strategies represent a powerful approach able to increase the therapeutic efficacy also highly reducing the overall toxicity. In this review, we will summarize recent progress in the field and discuss achieved objectives and optimization of aptamers as delivery carriers of short oligonucleotides.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.04.006
       
  • Repurposing excipients as active inhalation agents: The mannitol story
    • Authors: Sandra D. Anderson; Evangelia Daviskas; John D. Brannan; Hak Kim Chan
      Abstract: Publication date: Available online 5 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Sandra D. Anderson, Evangelia Daviskas, John D. Brannan, Hak Kim Chan
      The story of how we came to use inhaled mannitol to diagnose asthma and to treat cystic fibrosis began when we were looking for a surrogate for exercise as a stimulus to identify asthma. We had proposed that exercise-induced asthma was caused by an increase in osmolarity of the periciliary fluid. We found hypertonic saline to be a surrogate for exercise but an ultrasonic nebuliser was required. We produced a dry powder of sodium chloride but it proved unstable. We developed a spray dried preparation of mannitol and found that bronchial responsiveness to inhaling mannitol identified people with currently active asthma. We reasoned that mannitol had potential to replace the ‘osmotic’ benefits of exercise and could be used as a treatment to enhance mucociliary clearance in patients with cystic fibrosis. These discoveries were the start of a journey to develop several registered products that are in clinical use globally today.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.04.003
       
  • Transforming nanomedicine manufacturing toward Quality by Design and
           microfluidics
    • Authors: Stefano Colombo; Moritz Beck-Broichsitter; Johan Peter Bøtker; Martin Malmsten; Jukka Rantanen; Adam Bohr
      Abstract: Publication date: Available online 5 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Stefano Colombo, Moritz Beck-Broichsitter, Johan Peter Bøtker, Martin Malmsten, Jukka Rantanen, Adam Bohr
      Nanopharmaceuticals aim at translating the unique features of nano-scale materials into therapeutic products and consequently their development relies critically on the progression in manufacturing technology to allow scalable processes complying with process economy and quality assurance. The relatively high failure rate in translational nanopharmaceutical research and development, with respect to new products on the market, is at least partly due to immature bottom-up manufacturing development and resulting sub-optimal control of quality attributes in nanopharmaceuticals. Recently, quality-oriented manufacturing of pharmaceuticals has undergone an unprecedented change toward process and product development interaction. In this context, Quality by Design (QbD) aims to integrate product and process development resulting in an increased number of product applications to regulatory agencies and stronger proprietary defense strategies of process-based products. Although QbD can be applied to essentially any production approach, microfluidic production offers particular opportunities for QbD-based manufacturing of nanopharmaceuticals. Microfluidics provides unique design flexibility, process control and parameter predictability, and also offers ample opportunities for modular production setups, allowing process feedback for continuously operating production and process control. The present review aims at outlining emerging opportunities in the synergistic implementation of QbD strategies and microfluidic production in contemporary development and manufacturing of nanopharmaceuticals. In doing so, aspects of design and development, but also technology management, are reviewed, as is the strategic role of these tools for aligning nanopharmaceutical innovation, development, and advanced industrialization in the broader pharmaceutical field.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.04.004
       
  • The apparent competitive action of ECM proteases and cross-linking enzymes
           during fibrosis: applications to drug discovery
    • Authors: Nikolaos A. Afratis; Mordehay Klepfish; Nikos K. Karamanos; Irit Sagi
      Abstract: Publication date: Available online 5 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Nikolaos A. Afratis, Mordehay Klepfish, Nikos K. Karamanos, Irit Sagi
      Progressive loss of organ function in most organs is associated with fibrosis, a tissue state associated with abnormal matrix buildup. If highly progressive, the fibrotic process eventually leads to organ failure and death. Fibrosis is a basic connective tissue lesion defined by the increase in the amount of fibrillar extracellular matrix (ECM) components in a tissue or organ. In addition, intrinsic changes in important structural cells can induce the fibrotic response by regulating the differentiation, recruitment, proliferation and activation of extracellular matrix-producing myofibroblasts. ECM enzymes belonging to the family of matrix metalloproteinases (MMPs) and lysyl oxidases (LOXs) play a crucial role in ECM remodeling and regeneration. MMPs have a catalytic role in degradation of ECM, whereas LOX/LOXLs mediate ECM, especially collagen, cross-linking and stiffening. Importantly, enzymes from both families are elevated during the fibrotic response to tissue injury and its resolution. Yet, the apparent molecular competition or antagonistic activities of these enzyme families during the various stages of fibrosis is often overlooked. In this review, we discuss the diverse roles of MMPs and LOX/LOXL2 in chronic organ fibrosis. Finally, we review contemporary therapeutic strategies for fibrosis treatment, based on neutralization of MMP and LOX activity, as well as the development of novel drug delivery approaches.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.004
       
  • Microfluidics in nanoparticle drug delivery; From synthesis to
           pre-clinical screening
    • Authors: Jungho Ahn; Jihoon Ko; Somin Lee; James Yu; YongTae Kim; Noo Li Jeon
      Abstract: Publication date: Available online 5 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Jungho Ahn, Jihoon Ko, Somin Lee, James Yu, YongTae Kim, Noo Li Jeon
      Microfluidic technologies employ nano and microscale fabrication techniques to develop highly controllable and reproducible fluidic microenvironments. Utilizing microfluidics, lead compounds can be produced with the controlled physicochemical properties, characterized in a high-throughput fashion, and evaluated in in vitro biomimetic models of human organs; organ-on-a-chip. As a step forward from conventional in vitro culture methods, microfluidics shows promise in effective preclinical testing of nanoparticle-based drug delivery. This review presents a curated selection of state-of-the-art microfluidic platforms focusing on the fabrication, characterization, and assessment of nanoparticles for drug delivery applications. We also discuss the current challenges and future prospects of nanoparticle drug delivery development using microfluidics.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.04.001
       
  • Instructive microenvironments in skin wound healing: Biomaterials as
           signal releasing platforms
    • Authors: Oscar Castaño; Soledad Pérez-Amodio; Claudia Navarro; Miguel Ángel Mateos-Timoneda; Elisabeth Engel
      Abstract: Publication date: Available online 5 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Oscar Castaño, Soledad Pérez-Amodio, Claudia Navarro, Miguel Ángel Mateos-Timoneda, Elisabeth Engel
      Skin wound healing aims to repair and restore tissue through a multistage process that involves different cells and signalling molecules that regulate the cellular response and the dynamic remodelling of the extracellular matrix. Nowadays, several therapies that combine biomolecule signals (growth factors and cytokines) and cells are being proposed. However, a lack of reliable evidence of their efficacy, together with associated issues such as high costs, a lack of standardization, no scalable processes, and storage and regulatory issues, are hampering their application. In situ tissue regeneration appears to be a feasible strategy that uses the body's own capacity for regeneration by mobilizing host endogenous stem cells or tissue-specific progenitor cells to the wound site to promote repair and regeneration. The aim is to engineer instructive systems to regulate the spatio-temporal delivery of proper signalling based on the biological mechanisms of the different events that occur in the host microenvironment. This review describes the current state of the different signal cues used in wound healing and skin regeneration, and their combination with biomaterial supports to create instructive microenvironments for wound healing.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.012
       
  • Drug delivery systems and materials for wound healing applications
    • Authors: Saghi Saghazadeh; Chiara Rinoldi; Maik Schot; Sara Saheb Kashaf; Fatemeh Sharifi; Elmira Jalilian; Kristo Nuutila; Giorgio Giatsidis; Pooria Mostafalu; Hossein Derakhshandeh; Kan Yue; Wojciech Swieszkowski; Adnan Memic; Ali Tamayol; Ali Khademhosseini
      Abstract: Publication date: Available online 5 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Saghi Saghazadeh, Chiara Rinoldi, Maik Schot, Sara Saheb Kashaf, Fatemeh Sharifi, Elmira Jalilian, Kristo Nuutila, Giorgio Giatsidis, Pooria Mostafalu, Hossein Derakhshandeh, Kan Yue, Wojciech Swieszkowski, Adnan Memic, Ali Tamayol, Ali Khademhosseini
      Chronic, non-healing wounds place a significant burden on patients and healthcare systems, resulting in impaired mobility, limb amputation, or even death. Chronic wounds result from a disruption in the highly orchestrated cascade of events involved in wound closure. Significant advances in our understanding of the pathophysiology of chronic wounds have resulted in the development of drugs designed to target different aspects of the impaired processes. However, the hostility of the wound environment rich in degradative enzymes and its elevated pH, combined with differences in the time scales of different physiological processes involved in tissue regeneration require the use of effective drug delivery systems. In this review, we will first discuss the pathophysiology of chronic wounds and then the materials used for engineering drug delivery systems. Different passive and active drug delivery systems used in wound care will be reviewed. In addition, the architecture of the delivery platform and its ability to modulate drug delivery are discussed. Emerging technologies and the opportunities for engineering more effective wound care devices are also highlighted.
      Graphical abstract image

      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.04.008
       
  • Clinical indications for, and the future of, circulating tumor cells
    • Authors: Dominic H. Moon; Daniel P. Lindsay; Seungpyo Hong; Andrew Z. Wang
      Abstract: Publication date: Available online 5 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Dominic H. Moon, Daniel P. Lindsay, Seungpyo Hong, Andrew Z. Wang
      Circulating tumor cells (CTCs) are cells that have detached from the primary tumor and entered circulation with potential to initiate a site of metastasis. Currently, CTC detection using CellSearch is cleared by the Food and Drug Administration for monitoring metastatic breast, prostate, and colorectal cancers as a prognostic biomarker for progression-free and overall survival. Accumulating evidence suggests CTCs have similar prognostic value in other metastatic and non-metastatic settings. Current research efforts are focused on extending the utility of CTCs beyond a prognostic biomarker to help guide clinical decision-making. These include using CTCs as a screening tool for diagnosis, liquid biopsy for molecular profiling, predictive biomarker to specific therapies, and monitoring tool to assess response and guide changes to treatment. CTCs have unique advantages vs circulating tumor DNA in this endeavor. Indications for CTCs in daily practice will expand as isolation techniques improve and clinical studies validating their utility continue to grow.
      Graphical abstract image

      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.04.002
       
  • Controlled release technology for anti-angiogenesis treatment of posterior
           eye diseases: Current status and challenges
    • Authors: Chi Ming Laurence Lau; Yu Yu; Ghodsiehsadat Jahamir; Ying Chau
      Abstract: Publication date: Available online 4 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Chi Ming Laurence Lau, Yu Yu, Ghodsiehsadat Jahamir, Ying Chau
      Antiangiogenic therapeutics, such as corticosteroids, VEGF targeting antibodies and aptamers have been demonstrated effective in controlling retinal and choroidal neovascularization related vision loss. However, to manage the chronic conditions, it requires long term and frequent intravitreal injections of these drugs, resulting in poor patient compliance and suboptimal treatment. In addition, emerging drugs such as tyrosine kinase inhibitors and siRNAs received much expectations, but the late stage clinical trials encountered various obstacles. Controlled release technology could improve the existing treatment regimen by extending therapeutic duration, reducing risks and burdens caused by frequent injections, and enabling new drugs to overcome the hurdles of translation. Here, we give qualitative and quantitative discussions about the principle mechanisms of polymeric reservoir, polymeric matrix and hydrogel systems. We also reveal the design rationales of the existing drug delivery and release systems in preclinical and clinical stages. Lastly, the animal models of ocular angiogenesis diseases are critically reviewed, which could help to facilitate the translation of controlled release technologies from bench to bedside.
      Graphical abstract image

      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.013
       
  • Aptamer chemistry
    • Authors: Pascal Röthlisberger; Marcel Hollenstein
      Abstract: Publication date: Available online 4 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Pascal Röthlisberger, Marcel Hollenstein
      Aptamers are single-stranded DNA or RNA molecules capable of tightly binding to specific targets. These functional nucleic acids are obtained by an in vitro Darwinian evolution method coined SELEX (Systematic Evolution of Ligands by EXponential enrichment). Compared to their proteinaceous counterparts, aptamers offer a number of advantages including a low immunogenicity, a relative ease of large-scale synthesis at affordable costs with little or no batch-to-batch variation, physical stability, and facile chemical modification. These alluring properties have propelled aptamers into the forefront of numerous practical applications such as the development of therapeutic and diagnostic agents as well as the construction of biosensing platforms. However, commercial success of aptamers still proceeds at a weak pace. The main factors responsible for this delay are the susceptibility of aptamers to degradation by nucleases, their rapid renal filtration, suboptimal thermal stability, and the lack of functional group diversity. Here, we describe the different chemical methods available to mitigate these shortcomings. Particularly, we describe the chemical post-SELEX processing of aptamers to include functional groups as well as the inclusion of modified nucleoside triphosphates into the SELEX protocol. These methods will be illustrated with successful examples of chemically modified aptamers used as drug delivery systems, in therapeutic applications, and as biosensing devices.
      Graphical abstract image

      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.04.007
       
  • Insulin Delivery Systems Combined with Microneedle Technology
    • Authors: Xuan Jin; Dan Dan Zhu; Bo Zhi Chen; Mohammad Ashfaq; Xin Dong Guo
      Abstract: Publication date: Available online 29 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Xuan Jin, Dan Dan Zhu, Bo Zhi Chen, Mohammad Ashfaq, Xin Dong Guo
      Diabetes, a metabolic disorder of glucose, is a serious chronic disease and an important public health problem. Insulin is one of the hormones for modulating blood glucose level and the products of which is indispensable for most diabetes patients. Introducing microneedles (MNs) to insulin delivery is promising to pave the way for modulating glucose level noninvasively of diabetes patients, as which born to be painless, easy to handle and no need of any power supply. In this work, we review the process of insulin delivery systems (IDSs) based on MN technology in terms of two categories: drug free MNs and drug loaded MNs. Drug free MNs include solid MNs (“poke and patch”), hollow MNs (“poke and flow”) and reservoir-based swelling MNs (“poke and swell R-type”), and drug loaded MNs include coated MNs (“coat and poke”), dissolving MNs (“poke and release”) and insulin incorporated swelling MNs (“poke and swell I-type”). Majority researches of MN-based IDSs have been conducted by using hollow MNs or dissolving MNs, and almost all clinical trials for MN-based IDSs have employed hollow MNs. “Poke and patch” approach dramatically increase skin permeability compared to traditional transdermal patch, but MNs fabricated from silicon or metal may leave sharp waste in the skin and cause a safety issue. “Poke and flow” approach, similar to transitional subcutaneous (SC) injection, is capable of producing faster insulin absorption and action than SC injection but may associate with blockage, leakage and low flow rate. Coated MNs are able of retaining the activity of drug, which loaded in a solid phase, for a long time, however have been relatively less studied for insulin application as the low drug dosing. “Poke and release” approach leaves no biohazardous sharp medical waste and is capable of rapid drug release. “Poke and swell R-type” can be seen as a combination of “poke and flow” and “poke and patch” approach, while “poke and swell I-type” is an approach between “coat and poke” and “poke and release” approach. Insulin MNs are promising for painless diabetes therapeutics, and additional efforts for addressing fundamental issues including the drug loading, the PK/PD profile, the storage and the safety of insulin MNs will accelerate the clinical transformation.
      Graphical abstract image

      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.011
       
  • Transdermal immunomodulation: Principles, advances and perspectives
    • Authors: Zongmin Zhao; Anvay Ukidve; Anshuman Dasgupta; Samir Mitragotri
      Abstract: Publication date: Available online 29 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Zongmin Zhao, Anvay Ukidve, Anshuman Dasgupta, Samir Mitragotri
      Immunomodulation, manipulation of the immune responses towards an antigen, is a promising strategy to treat cancer, infectious diseases, allergies, and autoimmune diseases, among others. Unique features of the skin including the presence of tissue-resident immune cells, ease of access and connectivity to other organs makes it a unique target organ for immunomodulation. In this review, we summarize advances in transdermal delivery of agents for modulating the immune responses for vaccination as well as tolerization. The biological foundation of skin-based immunomodulation and challenges in its implementation are described. Technological approaches aimed at enhancing the delivery of immunomodulatory therapeutics into skin are also discussed in this review. Progress made in the treatment of several specific diseases including cancer, infections and allergy are discussed. Finally, this review discusses some practical considerations and offers some recommendations for future studies in the field of transdermal immunomodulation.
      Graphical abstract image

      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.010
       
  • Drug delivery to the lens for the management of cataracts
    • Authors: Thilini R. Thrimawithana; Ilva D. Rupenthal; Simon S. Räsch; Julie C. Lim; James D. Morton; Craig R. Bunt
      Abstract: Publication date: Available online 28 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Thilini R. Thrimawithana, Ilva D. Rupenthal, Simon S. Räsch, Julie C. Lim, James D. Morton, Craig R. Bunt
      Cataracts are one of the most prevalent diseases of the lens, affecting its transparency and are the leading cause of reversible blindness in the world. The clarity of the lens is essential for its normal physiological function of refracting light onto the retina. Currently there is no pharmaceutical treatment for prevention or cure of cataracts and surgery to replace the affected lens remains the gold standard in the management of cataracts. Pharmacological treatment for prevention of cataracts is hindered by many physiological barriers that must be overcome by a therapeutic agent to reach the avascular lens. Various therapeutic agents and formulation strategies are currently being investigated to prevent cataract formation as access to surgery is limited. This review provides a summary of recent research in the field of drug delivery to the lens for the management of cataracts including models used to study cataract treatments and discusses the future perspectives in the field.
      Graphical abstract image

      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.009
       
  • Delivery systems of current biologicals for the treatment of chronic
           cutaneous wounds and severe burns
    • Authors: Meilang Xue; Ruilong Zhao; Haiyan Lin; Christopher Jackson
      Abstract: Publication date: Available online 19 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Meilang Xue, Ruilong Zhao, Haiyan Lin, Christopher Jackson
      While wound therapy remains a clinical challenge in current medical practice, much effort has focused on developing biological therapeutic approaches. This paper presents a comprehensive review of delivery systems for current biologicals for the treatment of chronic wounds and severe burns. The biologicals discussed here include proteins such as growth factors and gene modifying molecules, which may be delivered to wounds free, encapsulated, or released from living systems (cells, skin grafts or skin equivalents) or biomaterials. Advances in biomaterial science and technologies have enabled the synthesis of delivery systems such as scaffolds, hydrogels and nanoparticles, designed to not only allow spatially and temporally controlled release of biologicals, but to also emulate the natural extracellular matrix microenvironment. These technologies represent an attractive field for regenerative wound therapy, by offering more personalised and effective treatments.
      Graphical abstract image

      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.002
       
  • Advances in microfluidics for lipid nanoparticles and extracellular
           vesicles and applications in drug delivery systems
    • Authors: Masatoshi Maeki; Niko Kimura; Yusuke Sato; Hideyoshi Harashima; Manabu Tokeshi
      Abstract: Publication date: Available online 19 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Masatoshi Maeki, Niko Kimura, Yusuke Sato, Hideyoshi Harashima, Manabu Tokeshi
      Lipid-based nanobiomaterials as liposomes and lipid nanoparticles (LNPs) are the most widely used nanocarriers for drug delivery systems (DDSs). Extracellular vesicles (EVs) and exosomes are also expected to be applied as DDS nanocarriers. The performance of nanomedicines relies on their components such as lipids, targeting ligands, encapsulated DNA, encapsulated RNA, and drugs. Recently, the importance of the nanocarrier sizes smaller than 100 nm is attracting attention as a means to improve the nanomedicine performance. Microfluidics and lab-on-a chip technologies make it possible to produce size-controlled LNPs by a simple continuous flow process and to separate EVs from blood samples by using a surface marker, ligand or electric charge, or by making a mass or particle size discrimination. Here, we overview recent advances in microfluidic devices and techniques for liposomes, LNPs and EVs and their applications for DDSs.
      Graphical abstract image

      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.008
       
  • In situ forming injectable hydrogels for drug delivery and wound repair
    • Authors: Robert Dimatteo; Nicole J. Darling; Tatiana Segura
      Abstract: Publication date: Available online 19 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Robert Dimatteo, Nicole J. Darling, Tatiana Segura
      Hydrogels have been utilized in regenerative applications for many decades because of their biocompatibility and similarity in structure to the native extracellular matrix. Initially, these materials were formed outside of the patient and implanted using invasive surgical techniques. However, advances in synthetic chemistry and materials science have now provided researchers with a library of techniques whereby hydrogel formation can occur in situ upon delivery through standard needles. This provides an avenue to minimally invasively deliver therapeutic payloads, fill complex tissue defects, and induce the regeneration of damaged portions of the body. In this review, we highlight these injectable therapeutic hydrogel biomaterials in the context of drug delivery and tissue regeneration for skin wound repair.
      Graphical abstract image

      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.007
       
  • Nanopharmaceuticals for wound healing – Lost in translation'
    • Authors: Mukul Ashtikar; Matthias G. Wacker
      Abstract: Publication date: Available online 19 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Mukul Ashtikar, Matthias G. Wacker
      Today, many of the newly developed pharmaceuticals and medical devices take advantage of nanotechnology and with a rising incidence of chronic diseases such as diabetes and cardiovascular disease, the number of patients afflicted globally with non-healing wounds is growing. This has created a requirement for improved therapies and wound care. However, converting the strategies applied in early research into new products is still challenging. Many of them fail to comply with the market requirements. This review discusses the legal and scientific challenges in the design of nanomedicines for wound healing. Are they lost in translation or is there a new generation of therapeutics in the pipeline?
      Graphical abstract image

      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.005
       
  • NanoVelcro rare-cell assays for detection and characterization of
           circulating tumor cells
    • Authors: Yu Jen Jan; Jie-Fu Chen; Yazhen Zhu; Yi-Tsung Lu; Szu Hao Chen; Howard Chung; Matthew Smalley; Yen-Wen Huang; Jiantong Dong; Hsiao-Hua Yu; James S. Tomlinson; Shuang Hou; Vatche G. Agopian; Edwin M. Posadas; Hsian-Rong Tseng
      Abstract: Publication date: Available online 15 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Yu Jen Jan, Jie-Fu Chen, Yazhen Zhu, Yi-Tsung Lu, Szu Hao Chen, Howard Chung, Matthew Smalley, Yen-Wen Huang, Jiantong Dong, Hsiao-Hua Yu, James S. Tomlinson, Shuang Hou, Vatche G. Agopian, Edwin M. Posadas, Hsian-Rong Tseng
      Circulating tumor cells (CTCs) are cancer cells shredded from either a primary tumor or a metastatic site and circulate in the blood as the potential cellular origin of metastasis. By detecting and analyzing CTCs, we will be able to noninvasively monitor disease progression in individual cancer patients and obtain insightful information for assessing disease status, thus realizing the concept of “tumor liquid biopsy”. However, it is technically challenging to identify CTCs in patient blood samples because of the extremely low abundance of CTCs among a large number of hematologic cells. In order to address this challenge, our research team at UCLA pioneered a unique concept of “NanoVelcro” cell-affinity substrates, in which CTC capture agent-coated nanostructured substrates were utilized to immobilize CTCs with remarkable efficiency. Four generations of NanoVelcro CTC assays have been developed over the past decade for a variety of clinical utilities. The 1st-gen NanoVelcro chips, composed of a silicon nanowire substrate (SiNS) and an overlaid microfluidic chaotic mixer, were created for CTC enumeration. The 2nd-gen NanoVelcro chips (i.e., NanoVelcro-LMD), based on polymer nanosubstrates, were developed for single-CTC isolation in conjunction with the use of the laser microdissection (LMD) technique. By grafting thermoresponsive polymer brushes onto SiNS, the 3rd-gen Thermoresponsive NanoVelcro chips have demonstrated the capture and release of CTCs at 37 and 4 °C respectively, thereby allowing for rapid CTC purification while maintaining cell viability and molecular integrity. Fabricated with boronic acid-grafted conducting polymer-based nanomaterial on chip surface, the 4th-gen NanoVelcro Chips (Sweet chip) were able to purify CTCs with well-preserved RNA transcripts, which could be used for downstream analysis of several cancer specific RNA biomarkers. In this review article, we will summarize the development of the four generations of NanoVelcro CTC Assays, and the clinical applications of each generation of devices.
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      PubDate: 2018-03-17T17:52:01Z
      DOI: 10.1016/j.addr.2018.03.006
       
  • Bioactive scaffolds based on elastin-like materials for wound healing
    • Authors: J. Carlos Rodríguez-Cabello; I. González de Torre; A. Ibañez-Fonzeca; M. Alonso
      Abstract: Publication date: Available online 15 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): J. Carlos Rodríguez-Cabello, I. González de Torre, A. Ibañez-Fonzeca, M. Alonso
      Wound healing is a complex process that, in healthy tissues, starts immediately after the injury. Even though it is a natural well-orchestrated process, large trauma wounds, or injuries caused by acids or other chemicals, usually produce a non-elastic deformed tissue that not only have biological reduced properties but a clear aesthetic effect. One of the main drawbacks of the scaffolds used for wound dressing is the lack of elasticity, driving to non-elastic and contracted tissues. In the last decades, elastin based materials have gained in importance as biomaterials for tissue engineering applications due to their good cyto- and bio-compatibility, their ease handling and design, production and modification. Synthetic elastin or elastin like-peptides (ELPs) are the two main families of biomaterials that try to mimic the outstanding properties of natural elastin, elasticity among others; although there are no in vivo studies that clearly support that these two families of elastin based materials improve the elasticity of the artificial scaffolds and of the regenerated skin. Within the next pages a review of the different forms (coacervates, fibres, hydrogels and biofunctionalized surfaces) in which these two families of biomaterials can be processed to be applied in the wound healing field have been done. Here, we explore the mechanical and biological properties of these scaffolds as well as the different in vivo approaches in which these scaffolds have been used.
      Graphical abstract image

      PubDate: 2018-03-17T17:52:01Z
      DOI: 10.1016/j.addr.2018.03.003
       
  • The suprachoroidal space as a route of administration to the posterior
           segment of the eye
    • Authors: Bryce Chiang; Jaehwan Jung; Mark Prausnitz
      Abstract: Publication date: Available online 12 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Bryce Chiang, Jaehwan Jung, Mark Prausnitz
      The suprachoroidal space (SCS) is a potential space between the sclera and choroid that traverses the circumference of the posterior segment of the eye. The SCS is an attractive site for drug delivery because it targets the choroid, retinal pigment epithelium and retina with high bioavailability, while maintaining low levels elsewhere in the eye. Indeed, phase III clinical trials are investigating the safety and efficacy of SCS drug delivery. Here, we review the anatomy and physiology of the SCS; methods to access the SCS; kinetics of SCS drug delivery; strategies to target within the SCS; current and potential clinical indications; and the safety and efficacy of this approach in preclinical animal studies and clinical trials.
      Graphical abstract image

      PubDate: 2018-03-17T17:52:01Z
      DOI: 10.1016/j.addr.2018.03.001
       
  • Corrigendum to ‘Tumor-targeting peptides from combinatorial libraries’
           [Adv Drug Deliv Rev.110–111 (2017) 13–37]
    • Authors: Ruiwu Liu; Xiaocen Li; Wenwu Xiao; Kit S. Lam
      Abstract: Publication date: Available online 9 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Ruiwu Liu, Xiaocen Li, Wenwu Xiao, Kit S. Lam


      PubDate: 2018-03-17T17:52:01Z
      DOI: 10.1016/j.addr.2018.02.005
       
  • Drug delivery and Epimorphic salamander-type mouse regeneration: A full
           parts and labor plan
    • Authors: Ellen Heber-Katz; Phillip Messersmith
      Abstract: Publication date: Available online 7 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Ellen Heber-Katz, Phillip Messersmith
      The capacity to regenerate entire body parts, tissues, and organs had generally been thought to be lost in evolution with very few exceptions (eg. the liver) surviving in mammals. The discovery of the MRL mouse and the elucidation of the underlying molecular pathway centering around hypoxia inducible factor, HIF-1α, has allowed a drug and materials approach to regeneration in mice and hopefully humans. The HIF-1α pathway is ancient and permitted the transition from unicellular to multicellular organisms. Furthermore, HIF-1α and its regulation by PHDs, important oxygen sensors in the cell, provides a perfect drug target. We review the historical background of regeneration biology, the discovery of the MRL mouse, and its underlying biology, and novel approaches to drugs, targets, and delivery systems.
      Graphical abstract image

      PubDate: 2018-03-17T17:52:01Z
      DOI: 10.1016/j.addr.2018.02.006
       
  • Tackling muscle fibrosis: From molecular mechanisms to next generation
           engineered models to predict drug delivery
    • Authors: S. Bersini; M. Gilardi; M. Mora; S. Krol; C. Arrigoni; C. Candrian; S. Zanotti; M. Moretti
      Abstract: Publication date: Available online 5 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): S. Bersini, M. Gilardi, M. Mora, S. Krol, C. Arrigoni, C. Candrian, S. Zanotti, M. Moretti
      Muscle fibrosis represents the end stage consequence of different diseases, among which muscular dystrophies, leading to severe impairment of muscle functions. Muscle fibrosis involves the production of several growth factors, cytokines and proteolytic enzymes and is strictly associated to inflammatory processes. Moreover, fibrosis causes profound changes in tissue properties, including increased stiffness and density, lower pH and oxygenation. Up to now, there is no therapeutic approach able to counteract the fibrotic process and treatments directed against muscle pathologies are severely impaired by the harsh conditions of the fibrotic environment. The design of new therapeutics thus need innovative tools mimicking the obstacles posed by the fibrotic environment to their delivery. This review will critically discuss the role of in vivo and 3D in vitro models in this context and the characteristics that an ideal model should possess to help the translation from bench to bedside of new candidate anti-fibrotic agents.
      Graphical abstract image

      PubDate: 2018-03-06T14:45:40Z
      DOI: 10.1016/j.addr.2018.02.009
       
  • Limiting angiogenesis to modulate scar formation
    • Authors: Stefanie Korntner; Christine Lehner; Renate Gehwolf; Andrea Wagner; Moritz Grütz; Nadja Kunkel; Herbert Tempfer; Andreas Traweger
      Abstract: Publication date: Available online 3 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Stefanie Korntner, Christine Lehner, Renate Gehwolf, Andrea Wagner, Moritz Grütz, Nadja Kunkel, Herbert Tempfer, Andreas Traweger
      Angiogenesis, the process of new blood vessel formation from existing blood vessels, is a key aspect of virtually every repair process. During wound healing an extensive, but immature and leaky vascular plexus forms which is subsequently reduced by regression of non-functional vessels. More recent studies indicate that uncontrolled vessel growth or impaired vessel regression as a consequence of an excessive inflammatory response can impair wound healing, resulting in scarring and dysfunction. However, in order to elucidate targetable factors to promote functional tissue regeneration we need to understand the molecular and cellular underpinnings of physiological angiogenesis, ranging from induction to resolution of blood vessels. Especially for avascular tissues (e.g. cornea, tendon, ligament, cartilage, etc.), limiting rather than boosting vessel growth during wound repair potentially is beneficial to restore full tissue function and may result in favourable long-term healing outcomes.
      Graphical abstract image

      PubDate: 2018-03-06T14:45:40Z
      DOI: 10.1016/j.addr.2018.02.010
       
  • Responsive triggering systems for delivery in chronic wound healing
    • Authors: Mangesh Morey; Abhay Pandit
      Abstract: Publication date: Available online 2 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Mangesh Morey, Abhay Pandit
      Non-communicable diseases including cancer, cardiovascular disease, diabetes, and neuropathy are chronic in nature. Treatment of these diseases with traditional delivery systems is limited due to lack of site-specificity, non-spatiotemporal release and insufficient doses. Numerous responsive delivery systems which respond to both physiological and external stimuli have been reported in the literature. However, effective strategies incorporating a multifactorial approach are required to control these complex wounds. This can be achieved by fabricating spatiotemporal release systems, multimodal systems or dual/multi-stimuli responsive delivery systems loaded with one or more bioactive components. Critically, these next generation stimuli responsive delivery systems that are at present not feasible are required to treat chronic wounds. This review provides a critical assessment of recent developments in the field of responsive delivery systems, highlighting their limitations and providing a perspective on how these challenges can be overcome.
      Graphical abstract image

      PubDate: 2018-03-06T14:45:40Z
      DOI: 10.1016/j.addr.2018.02.008
       
  • Lumican as a multivalent effector in wound healing
    • Authors: Konstantina Karamanou; Gwenn Perrot; Francois-Xavier Maquart; Stéphane Brézillon
      Abstract: Publication date: Available online 1 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Konstantina Karamanou, Gwenn Perrot, Francois-Xavier Maquart, Stéphane Brézillon
      Wound healing, a complex physiological process, is responsible for tissue repair after exposure to destructive stimuli, without resulting in complete functional regeneration. Injuries can be stromal or epithelial, and most cases of wound repair have been studied in the skin and cornea. Lumican, a small leucine-rich proteoglycan, is expressed in the extracellular matrices of several tissues, such as the cornea, cartilage, and skin. This molecule has been shown to regulate collagen fibrillogenesis, keratinocyte phenotypes, and corneal transparency modulation. Lumican is also involved in the extravasation of inflammatory cells and angiogenesis, which are both critical in stromal wound healing. Lumican is the only member of the small leucine-rich proteoglycan family expressed by the epithelia during wound healing. This review summarizes the importance of lumican in wound healing and potential methods of lumican drug delivery to target wound repair are discussed. The involvement of lumican in corneal wound healing is described based on in vitro and in vivo models, with critical emphasis on its underlying mechanisms of action. Similarly, the expression and role of lumican in the healing of other tissues are presented, with emphasis on skin wound healing. Overall, lumican promotes normal wound repair and broadens new therapeutic perspectives for impaired wound healing.
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      PubDate: 2018-03-06T14:45:40Z
      DOI: 10.1016/j.addr.2018.02.011
       
  • Wound healing related agents: Ongoing research and perspectives
    • Authors: Konstantina Kaplani; Stamatina Koutsi; Vasileios Armenis; Foteini G. Skondra; Nickolas Karantzelis; Spyridon Champeris Tsaniras; Stavros Taraviras
      Abstract: Publication date: Available online 1 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Konstantina Kaplani, Stamatina Koutsi, Vasileios Armenis, Foteini G. Skondra, Nickolas Karantzelis, Spyridon Champeris Tsaniras, Stavros Taraviras
      Wound healing response plays a central part in chronic inflammation, affecting millions of people worldwide. It is a dynamic process that can lead to fibrosis, if tissue damage is irreversible and wound resolution is not attained. It is clear that there is a tight interconnection among wound healing, fibrosis and a variety of chronic disease conditions, demonstrating the heterogeneity of this pathology. Based on our further understanding of the cellular and molecular mechanisms underpinning tissue repair, new therapeutic approaches have recently been developed that target different aspects of the wound healing process and fibrosis. Nevertheless, several issues still need to be taken into consideration when designing modern wound healing drug delivery formulations. In this review, we highlight novel pharmacological agents that hold promise for targeting wound repair and fibrosis. We also focus on drug-delivery systems that may enhance current and future therapies.
      Graphical abstract image

      PubDate: 2018-03-06T14:45:40Z
      DOI: 10.1016/j.addr.2018.02.007
       
  • 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.
      Graphical abstract image

      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.
      Graphical abstract image

      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.
      Graphical abstract image

      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.
      Graphical abstract image

      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.
      Graphical abstract image

      PubDate: 2018-02-05T09:38:17Z
      DOI: 10.1016/j.addr.2018.01.012
       
  • 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.
      Graphical abstract image

      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.019
       
 
 
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