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Journal Cover
Advanced Drug Delivery Reviews
Journal Prestige (SJR): 4.09
Citation Impact (citeScore): 13
Number of Followers: 136  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0169-409X
Published by Elsevier Homepage  [3163 journals]
  • Practical guidelines for the characterization and quality control of pure
           drug nanoparticles and nano-cocrystals in the pharmaceutical industry
    • Abstract: Publication date: Available online 18 June 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Leena Peltonen
      The number of poorly soluble drug candidates is increasing, and this is also seen in the research interest towards drug nanoparticles and (nano-)cocrystals; improved solubility is the most important application of these nanosystems. In order to confirm the functionality of these nanoparticles throughout their lifecycle, repeatability of the formulation processes, functional performance of the formed systems in pre-determined way and system stability, a thorough physicochemical understanding with the aid of necessary analytical techniques is needed. Even very minor deviations in for example particle size or size deviation in nanoscale can alter the product bioavailability, and the effect is even more dramatic with the smallest particle size fractions. Also, small particle size sets special requirements for the analytical techniques. In this review most important physicochemical properties of drug nanocrystals and nano-cocrystals are presented, suitable analytical techniques, their pros and cons, are described with the extra input on practical point of view.
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      PubDate: 2018-06-20T14:38:39Z
       
  • Local delivery of adenosine receptor agonists to promote bone regeneration
           and defect healing
    • Abstract: Publication date: Available online 18 June 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Christopher D. Lopez, Jonathan M. Bekisz, Carmen Corciulo, Aranzazu Mediero, Paulo G. Coelho, Lukasz Witek, Roberto L. Flores, Bruce N. Cronstein
      Adenosine receptor activation has been investigated as a potential therapeutic approach to heal bone. Bone has enhanced regenerative potential when influenced by either direct or indirect adenosine receptor agonism. As investigators continue to elucidate how adenosine influences bone cell homeostasis at the cellular and molecular levels, a small but growing body of literature has reported successful in vivo applications of adenosine delivery. This review summarizes the role adenosine receptor ligation plays in osteoblast and osteoclast biology and remodeling/regeneration. It also reports on all the modalities described in the literature at this point for delivery of adenosine through in vivo models for bone healing and regeneration.
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      PubDate: 2018-06-20T14:38:39Z
       
  • Microphysiological systems meet hiPSC technology – New tools for disease
           modeling of liver infections in basic research and drug development
    • Abstract: Publication date: Available online 15 June 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Martin Raasch, Enrico Fritsche, Andreas Kurtz, Michael Bauer, Alexander S. Mosig
      Complex cell culture models such as microphysiological models (MPS) mimicking human liver functionality in vitro are in the spotlight as alternative to conventional cell culture and animal models. Promising techniques like microfluidic cell culture or micropatterning by 3D bioprinting are gaining increasing importance for the development of MPS to address the needs for more predictivity and cost efficiency. In this context, human induced pluripotent stem cells (hiPSCs) offer new perspectives for the development of advanced liver-on-chip systems by recreating an in vivo like microenvironment that supports the reliable differentiation of hiPSCs to hepatocyte-like cells (HLC). In this review we will summarize current protocols of HLC generation and highlight recently established MPS suitable to resemble physiological hepatocyte function in vitro. In addition, we are discussing potential applications of liver MPS for disease modeling related to systemic or direct liver infections and the use of MPS in testing of new drug candidates.
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      PubDate: 2018-06-18T14:37:22Z
       
  • Repurposing drugs as inhaled therapies in asthma
    • Abstract: Publication date: Available online 12 June 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Sandra D. Anderson
      For the first 40 years of the 20th century treatment for asthma occurred in response to an asthma attack. The treatments were given by injection or orally and included the adrenergic agonists adrenalin/epinephrine and ephedrine and a phosphodiesterase inhibitor theophylline. Epinephrine became available as an aerosol in 1930. After 1945, isoprenaline, a non-selective beta agonist, became available for oral use but it was most widely used by inhalation. Isoprenaline was short-acting with unwanted cardiac effects. More selective beta agonists, with a longer duration of action and fewer side-effects became available, including orciprenaline in 1967, salbutamol in 1969 and terbutaline in 1970. The inhaled steroid beclomethasone was available by 1972 and budesonide by 1982. Spirometry alone and in response to exercise was used to assess efficacy and duration of action of these drugs for the acute benefits of beta2 agonists and the chronic benefits of corticosteroids. Early studies comparing oral and aerosol beta2 agonists found equivalence in bronchodilator effect but the aerosol treatment was superior in preventing exercise-induced bronchoconstriction. Inhaled drugs are now widely used including the long-acting beta2 agonists, salmeterol and formoterol, and the corticosteroids, fluticasone, ciclesonide, mometasone and triamcinolone, that act locally and have low systemic bio-availability. Repurposing drugs as inhaled therapies permitted direct delivery of low doses of drug to the site of action reducing the incidence of unwanted side-effects and permitting the prophylactic treatment of asthma.
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      PubDate: 2018-06-18T14:37:22Z
       
  • Wound healing and scar wars
    • Abstract: Publication date: April 2018
      Source:Advanced Drug Delivery Reviews, Volume 129
      Author(s): Eugenia Pugliese, João Q. Coentro, Michael Raghunath, Dimitrios I. Zeugolis


      PubDate: 2018-06-18T14:37:22Z
       
  • Insights into the key roles of epigenetics in matrix
           macromolecules-associated wound healing
    • Abstract: Publication date: April 2018
      Source:Advanced Drug Delivery Reviews, Volume 129
      Author(s): Zoi Piperigkou, Martin Götte, Achilleas D. Theocharis, Nikos K. Karamanos
      Extracellular matrix (ECM) is a dynamic network of macromolecules, playing a regulatory role in cell functions, tissue regeneration and remodeling. Wound healing is a tissue repair process necessary for the maintenance of the functionality of tissues and organs. This highly orchestrated process is divided into four temporally overlapping phases, including hemostasis, inflammation, proliferation and tissue remodeling. The dynamic interplay between ECM and resident cells exerts its critical role in many aspects of wound healing, including cell proliferation, migration, differentiation, survival, matrix degradation and biosynthesis. Several epigenetic regulatory factors, such as the endogenous non-coding microRNAs (miRNAs), are the drivers of the wound healing response. microRNAs have pivotal roles in regulating ECM composition during wound healing and dermal regeneration. Their expression is associated with the distinct phases of wound healing and they serve as target biomarkers and targets for systematic regulation of wound repair. In this article we critically present the importance of epigenetics with particular emphasis on miRNAs regulating ECM components (i.e. glycoproteins, proteoglycans and matrix proteases) that are key players in wound healing. The clinical relevance of miRNA targeting as well as the delivery strategies designed for clinical applications are also presented and discussed.

      PubDate: 2018-06-18T14:37:22Z
       
  • Integrins in wound healing, fibrosis and tumor stroma: High potential
           targets for therapeutics and drug delivery
    • Abstract: Publication date: April 2018
      Source:Advanced Drug Delivery Reviews, Volume 129
      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, means 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 ligands are described.
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      PubDate: 2018-06-18T14:37:22Z
       
  • MicroRNAs in the pathogenesis and treatment of progressive liver injury in
           NAFLD and liver fibrosis
    • Abstract: Publication date: April 2018
      Source:Advanced Drug Delivery Reviews, Volume 129
      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 in 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: 2018-06-18T14:37:22Z
       
  • Engineered cell and tissue models of pulmonary fibrosis
    • Abstract: Publication date: April 2018
      Source:Advanced Drug Delivery Reviews, Volume 129
      Author(s): Aswin Sundarakrishnan, Ying Chen, Lauren D. Black, Bree B. Aldridge, David L. Kaplan
      Pulmonary fibrosis includes several lung disorders characterized by scar formation and Idiopathic Pulmonary Fibrosis (IPF) is a particularly severe form of pulmonary fibrosis of unknown etiology with a mean life expectancy of 3years' post-diagnosis. Treatments for IPF are limited to two FDA approved drugs, pirfenidone and nintedanib. Most lead candidate drugs that are identified in pre-clinical animal studies fail in human clinical trials. Thus, there is a need for advanced humanized in vitro models of the lung to improve candidate treatments prior to moving to human clinical trials. The development of 3D tissue models has created systems capable of emulating human lung structure, function, and cell and matrix interactions. The specific models accomplish these features and preliminary studies conducted using some of these systems have shown potential for in vitro anti-fibrotic drug testing. Further characterization and improvements will enable these tissue models to extend their utility for in vitro drug testing, to help identify signaling pathways and mechanisms for new drug targets, and potentially reduce animal models as standard pre-clinical models of study. In the current review, we contrast different in vitro models based on increasing dimensionality (2D, 2.5D and 3D), with added focus on contemporary 3D pulmonary models of fibrosis.
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      PubDate: 2018-06-18T14:37:22Z
       
  • Fibrin-based delivery strategies for acute and chronic wound healing
    • Abstract: Publication date: April 2018
      Source:Advanced Drug Delivery Reviews, Volume 129
      Author(s): P. Heher, S. Mühleder, R. Mittermayr, H. Redl, P. Slezak
      Fibrin, a natural hydrogel, is the end product of the physiological blood coagulation cascade and naturally involved in wound healing. Beyond its role in hemostasis, it acts as a local reservoir for growth factors and as a provisional matrix for invading cells that drive the regenerative process. Its unique intrinsic features do not only promote wound healing directly via modulation of cell behavior but it can also be fine-tuned to evolve into a delivery system for sustained release of therapeutic biomolecules, cells and gene vectors. To further augment tissue regeneration potential, current strategies exploit and modify the chemical and physical characteristics of fibrin to employ combined incorporation of several factors and their timed release. In this work we show advanced therapeutic approaches employing fibrin matrices in wound healing and cover the many possibilities fibrin offers to the field of regenerative medicine.
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      PubDate: 2018-06-18T14:37:22Z
       
  • Electroactive biomaterials: Vehicles for controlled delivery of
           therapeutic agents for drug delivery and tissue regeneration
    • Abstract: Publication date: April 2018
      Source:Advanced Drug Delivery Reviews, Volume 129
      Author(s): Biranche Tandon, Adrián Magaz, Richard Balint, Jonny J. Blaker, Sarah H. Cartmell
      Electrical stimulation for delivery of biochemical agents such as genes, proteins and RNA molecules amongst others, holds great potential for controlled therapeutic delivery and in promoting tissue regeneration. Electroactive biomaterials have the capability of delivering these agents in a localized, controlled, responsive and efficient manner. These systems have also been combined for the delivery of both physical and biochemical cues and can be programmed to achieve enhanced effects on healing by establishing control over the microenvironment. This review focuses on current state-of-the-art research in electroactive-based materials towards the delivery of drugs and other therapeutic signalling agents for wound care treatment. Future directions and current challenges for developing effective electroactive approach based therapies for wound care are discussed.
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      PubDate: 2018-06-18T14:37:22Z
       
  • Nanomedicines and gene therapy for the delivery of growth factors to
           improve perfusion and oxygenation in wound healing
    • Abstract: Publication date: April 2018
      Source:Advanced Drug Delivery Reviews, Volume 129
      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: 2018-06-18T14:37:22Z
       
  • Delivery of cellular factors to regulate bone healing
    • Abstract: Publication date: April 2018
      Source:Advanced Drug Delivery Reviews, Volume 129
      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.
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      PubDate: 2018-06-18T14:37:22Z
       
  • Targeting renal fibrosis: Mechanisms and drug delivery systems
    • Abstract: Publication date: April 2018
      Source:Advanced Drug Delivery Reviews, Volume 129
      Author(s): Madalina V. Nastase, Jinyang Zeng-Brouwers, Malgorzata Wygrecka, Liliana Schaefer
      Renal fibrosis is the common outcome of many chronic kidney diseases (CKD) independent of the underlying etiology. Despite a host of promising experimental data, currently available strategies only ameliorate or delay the progression of CKD but do not reverse fibrosis. One of the major impediments of translating novel antifibrotic strategies from bench to bedside is due to the intricacies of the drug delivery process. In this review, we briefly describe mechanisms of renal fibrosis and methods of drug transfer into the kidney. Various tools used in gene therapy to administer nucleic acids in vivo are discussed. Furthermore, we review the modes of action of protein- or peptide-based drugs with target-specific antibodies and cytokines incorporated in hydrogels. Additionally, we assess an intriguing new method to deliver drugs specifically to tubular epithelial cells via conjugation with ligands binding to the megalin receptor. Finally, plant-derived compounds with antifibrotic properties are also summarized.
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      PubDate: 2018-06-18T14:37:22Z
       
  • miRNA delivery for skin wound healing
    • Abstract: Publication date: April 2018
      Source:Advanced Drug Delivery Reviews, Volume 129
      Author(s): Zhao Meng, Dezhong Zhou, Yongsheng Gao, Ming Zeng, Wenxin Wang
      The wound healing has remained a worldwide challenge as one of significant public health problems. Pathological scars and chronic wounds caused by injury, aging or diabetes lead to impaired tissue repair and regeneration. Due to the unique biological wound environment, the wound healing is a highly complicated process, efficient and targeted treatments are still lacking. Hence, research-driven to discover more efficient therapeutics is a highly urgent demand. Recently, the research results have revealed that microRNA (miRNA) is a promising tool in therapeutic and diagnostic fields because miRNA is an essential regulator in cellular physiology and pathology. Therefore, new technologies for wound healing based on miRNA have been developed and miRNA delivery has become a significant research topic in the field of gene delivery.
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      PubDate: 2018-06-18T14:37:22Z
       
  • Drug delivery and tissue engineering to promote wound healing in the
           immunocompromised host: Current challenges and future directions
    • Abstract: Publication date: April 2018
      Source:Advanced Drug Delivery Reviews, Volume 129
      Author(s): Alexander M. Tatara, Dimitrios P. Kontoyiannis, Antonios G. Mikos
      As regenerative medicine matures as a field, more promising technologies are being translated from the benchtop to the clinic. However, many of these strategies are designed with otherwise healthy hosts in mind and validated in animal models without other co-morbidities. In reality, many of the patient populations benefiting from drug delivery and tissue engineering-based devices to enhance wound healing also have significant underlying immunodeficiency. Specifically, patients suffering from diabetes, malignancy, human immunodeficiency virus, post-organ transplantation, and other compromised states have significant pleotropic immune defects that affect wound healing. In this work, we review the role of different immune cells in the regenerative process, highlight the effect of several common immunocompromised states on wound healing, and discuss different drug delivery strategies for overcoming immunodeficiencies.
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      PubDate: 2018-06-18T14:37:22Z
       
  • Repurposing of statins via inhalation to treat lung inflammatory
           conditions
    • Authors: Peta Bradbury; Daniela Traini; Alaina J. Ammit; Paul M. Young; Hui Xin Ong
      Abstract: Publication date: Available online 8 June 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Peta Bradbury, Daniela Traini, Alaina J. Ammit, Paul M. Young, Hui Xin Ong
      Despite many therapeutic advancements over the past decade, the continued rise in chronic inflammatory lung diseases incidence has driven the need to identify and develop new therapeutic strategies, with superior efficacy to treat these diseases. Statins are one class of drug that could potentially be repurposed as an alternative treatment for chronic lung diseases. They are currently used to treat hypercholesterolemia by inhibiting the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, that catalyses the rate limiting step in the mevalonate biosynthesis pathway, a key intermediate in cholesterol metabolism. Recent research has identified statins to have other protective pleiotropic properties including anti-inflammatory, anti-oxidant, muco-inhibitory effects that may be beneficial for the treatment of chronic inflammatory lung diseases. However, clinical studies have yielded conflicting results. This review will summarise some of the current evidences for statins pleiotropic effects that could be applied for the treatment of chronic inflammatory lung diseases, their mechanisms of actions, and the potential to repurpose statins as an inhaled therapy, including a detailed discussion on their different physical-chemical properties and how these characteristics could ultimately affect treatment efficacies. The repurposing of statins from conventional anti-cholesterol oral therapy to inhaled anti-inflammatory formulation is promising, as it provides direct delivery to the airways, reduced risk of side effects, increased bioavailability and tailored physical-chemical properties for enhanced efficacy.
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      PubDate: 2018-06-11T02:52:49Z
      DOI: 10.1016/j.addr.2018.06.005
       
  • Inhalation of repurposed drugs to treat pulmonary hypertension
    • Authors: Tobias Gessler
      Abstract: Publication date: Available online 8 June 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Tobias Gessler
      Pulmonary arterial hypertension (PAH) is a rare, but severe and life-threatening disease characterized by vasoconstriction and remodeling of the pulmonary arterioles, leading to progressive increase in pulmonary vascular resistance and ultimately to right-heart failure. In the last two decades, significant progress in treatment of PAH has been made, with currently 12 drugs approved for targeted therapy. Among these, the stable prostacyclin analogues iloprost and treprostinil have been repurposed for inhalation. The paper highlights the development of the two drugs emphasizing the rationale and advantages of the inhalative approach. Despite substantial advances in the specific, mainly vasodilatory PAH therapy, disease progression is mostly inevitable and mortality remains unacceptably high. Thus, introduction of new drugs targeting the cancer-like remodeling of the diseased pulmonary arteries is urgently needed. Inhalation offers pulmonary selectivity and will hopefully pioneer the repurposing of novel highly potent drugs for effective aerosol therapy of PAH.
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      PubDate: 2018-06-08T09:59:24Z
      DOI: 10.1016/j.addr.2018.06.003
       
  • Repurposing of gamma interferon via inhalation delivery
    • Authors: Gerald C. Smaldone
      Abstract: Publication date: Available online 7 June 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Gerald C. Smaldone
      Pulmonary diseases frequently involve imbalances in immunity. The inability to control bacteria in tuberculosis is a failed response to a pathogen. Idiopathic pulmonary fibrosis (IPF), a progressive fibrotic lung disease, can lead to respiratory failure and death within 3 years of diagnosis. Chronic obstructive pulmonary disease (COPD) progresses until death and in recent years has been labeled an autoimmune disease. Proposed mechanistic pathways of pathophysiology involve uncontrolled healing governed by pro-fibrotic cytokines that are unresponsive to the standard anti-inflammatory agents (e.g., corticosteroids). Interferon-γ (IFN-γ), currently delivered as a subcutaneous injection for chronic granulomatous disease and osteopetrosis, is a cytokine that can stimulate macrophage function and inhibit fibrotic pathways. In recent studies, our group has repurposed IFN-γ as an inhaled aerosol, targeted directly to the lung to treat a host of diseases affected by dysregulated immunity. At present, we have studied its potential in treating tuberculosis and IPF. In a controlled clinical trial in tuberculosis, inhaled IFN-γ was effective while parenteral IFN-γ was not, indicating that macrophages can be effectively immune-stimulated by aerosol therapy. A similar approach has been taken in IPF. In a two-year safety study treating patients with IPF, the drug was safe and the pretreatment decline in pulmonary function was reversed. Furthermore, the same fibrotic pathways active in the lung parenchyma in IPF may be at fault in the airways of COPD patients. These experiences warrant the continued evaluation of inhaled IFN-γ in human clinical trials.
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      PubDate: 2018-06-08T09:59:24Z
      DOI: 10.1016/j.addr.2018.06.004
       
  • Progress, obstacles, and limitations in the use of stem cells in
           organ-on-a-chip models
    • Authors: Alexa Wnorowski; Huaxiao Yang; Joseph C. Wu
      Abstract: Publication date: Available online 6 June 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Alexa Wnorowski, Huaxiao Yang, Joseph C. Wu
      In recent years, drug development costs have soared, primarily due to the failure of preclinical animal and cell culture models, which do not directly translate to human physiology. Organ-on-a-chip (OOC) is a burgeoning technology with the potential to revolutionize disease modeling, drug discovery, and toxicology research by strengthening the relevance of culture-based models while reducing costly animal studies. Although OOC models can incorporate a variety of tissue sources, the most robust and relevant OOC models going forward will include stem cells. In this review, we will highlight the benefits of stem cells as a tissue source while considering current limitations to their complete and effective implementation into OOC models.
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      PubDate: 2018-06-08T09:59:24Z
      DOI: 10.1016/j.addr.2018.06.001
       
  • Engineered delivery strategies for enhanced control of growth factor
           activities in wound healing
    • Authors: Yiming Niu; Qiu Li; Ya Ding; Lei Dong; Chunming Wang
      Abstract: Publication date: Available online 5 June 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Yiming Niu, Qiu Li, Ya Ding, Lei Dong, Chunming Wang
      Growth factors (GFs) are versatile signalling molecules that orchestrate the dynamic, multi-stage process of wound healing. Delivery of exogenous GFs to the wound milieu to mediate healing in an active, physiologically-relevant manner has shown great promise in laboratories; however, the inherent instability of GFs, accompanied with numerous safety, efficacy and cost concerns, has hindered the clinical success of GF delivery. In this article, we highlight that the key to overcoming these challenges is to enhance the control of the activities of GFs throughout the delivering process. We summarise the recent strategies based on biomaterials matrices and molecular engineering, which aim to improve the conditions of GFs for delivery (at the ‘supply’ end of the delivery), increase the stability and functions of GFs in extracellular matrix (in transportation to target cells), as well as enhance the GFs/receptor interaction on the cell membrane (at the ‘destination’ end of the delivery). Many of these investigations have led to encouraging outcomes in various in vitro and in vivo regenerative models with considerable translational potential.
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      PubDate: 2018-06-08T09:59:24Z
      DOI: 10.1016/j.addr.2018.06.002
       
  • Reduction-sensitive polymeric nanomedicines: An emerging multifunctional
           platform for targeted cancer therapy
    • Authors: Huanli Sun; Yifan Zhang Zhiyuan Zhong
      Abstract: Publication date: Available online 24 May 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Huanli Sun, Yifan Zhang, Zhiyuan Zhong
      The development of smart delivery systems that are robust in circulation and quickly release drugs following selective internalization into target cancer cells is a key to precision cancer therapy. Interestingly, reduction-sensitive polymeric nanomedicines showing high plasma stability and triggered cytoplasmic drug release behavior have recently emerged as one of the most exciting platforms for targeted delivery of various anticancer drugs including small chemical drugs, proteins, and nucleic acids. In vivo studies in varying tumor models reveal that these reduction-sensitive multifunctional nanomedicines outperform the currently used clinical formulations and reduction-insensitive counterparts, bringing about not only significantly enhanced tumor selectivity, accumulation and inhibition efficacy but also markedly reduced systemic toxicity and improved therapeutic index. In this review, we will highlight the cutting-edge advancement with a focus on in vivo performances as well as future perspectives on reduction-sensitive polymeric nanomedicines for targeted cancer therapy.
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      PubDate: 2018-05-28T11:04:11Z
       
  • 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.
      Graphical abstract image

      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.
      Graphical abstract image

      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.
      Graphical abstract image

      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.
      Graphical abstract image

      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
       
  • 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.
      Graphical abstract image

      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
       
  • 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
       
  • 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
       
  • 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.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.04.007
       
  • 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
       
  • 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?
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.005
       
  • 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
       
  • 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.
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      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
       
  • 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
       
  • 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
       
 
 
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