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Journal Cover Advanced Drug Delivery Reviews
  [SJR: 5.2]   [H-I: 222]   [132 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0169-409X
   Published by Elsevier Homepage  [3049 journals]
  • ADDR Editor’s Collection 2017
    • Authors: Hamidreza Ghandehari
      First page: 1
      Abstract: Publication date: 1 December 2017
      Source:Advanced Drug Delivery Reviews, Volume 122
      Author(s): Hamidreza Ghandehari


      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.11.009
      Issue No: Vol. 122 (2017)
       
  • The battle of “nano” paclitaxel
    • Authors: Alexandros Marios Sofias; Michael Dunne; Gert Storm; Christine Allen
      Pages: 20 - 30
      Abstract: Publication date: 1 December 2017
      Source:Advanced Drug Delivery Reviews, Volume 122
      Author(s): Alexandros Marios Sofias, Michael Dunne, Gert Storm, Christine Allen
      Paclitaxel (PTX) is one of the three most widely used chemotherapeutic agents, together with doxorubicin and cisplatin, and is first or second line treatment for several types of cancers. In 2000, Taxol, the conventional formulation of PTX, became the best-selling cancer drug of all time with annual sales of 1.6 billion. In 2005, the introduction of the albumin-based formulation of PTX, known as Abraxane, ended Taxol's monopoly of the PTX market. Abraxane's ability to push the Taxol innovator and generic formulations aside attracted fierce competition amongst competitors worldwide to develop their own unique, new and improved formulation of PTX. At this time there are at least 18 companies focused on pre-clinical and/or clinical development of nano-formulations of PTX. These pharmaceutical companies are investing substantial capital to capture a share of the lucrative global PTX market. It is hoped that any formulation that dominates the market will result in tangible benefits to patients in terms of both survival and quality of life. Given all of this activity, here we address the question: Who is going to win the battle of “nano” paclitaxel?
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.02.003
      Issue No: Vol. 122 (2017)
       
  • Nanoparticles for drug delivery to the anterior segment of the eye
    • Authors: Dileep R. Janagam; Linfeng Wu; Tao L. Lowe
      Pages: 31 - 64
      Abstract: Publication date: 1 December 2017
      Source:Advanced Drug Delivery Reviews, Volume 122
      Author(s): Dileep R. Janagam, Linfeng Wu, Tao L. Lowe
      Commercially available ocular drug delivery systems are effective but less efficacious to manage diseases/disorders of the anterior segment of the eye. Recent advances in nanotechnology and molecular biology offer a great opportunity for efficacious ocular drug delivery for the treatments of anterior segment diseases/disorders. Nanoparticles have been designed for preparing eye drops or injectable solutions to surmount ocular obstacles faced after administration. Better drug pharmacokinetics, pharmacodynamics, non-specific toxicity, immunogenicity, and biorecognition can be achieved to improve drug efficacy when drugs are loaded in the nanoparticles. Despite the fact that a number of review articles have been published at various points in the past regarding nanoparticles for drug delivery, there is not a review yet focusing on the development of nanoparticles for ocular drug delivery to the anterior segment of the eye. This review fills in the gap and summarizes the development of nanoparticles as drug carriers for improving the penetration and bioavailability of drugs to the anterior segment of the eye.
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.04.001
      Issue No: Vol. 122 (2017)
       
  • Molecular links among non-biodegradable nanoparticles, reactive oxygen
           species, and autophagy
    • Authors: Uche C. Anozie; Paul Dalhaimer
      Pages: 65 - 73
      Abstract: Publication date: 1 December 2017
      Source:Advanced Drug Delivery Reviews, Volume 122
      Author(s): Uche C. Anozie, Paul Dalhaimer
      For nanoparticles to be successful in combating diseases in the clinic in the 21st century and beyond, they must localize to target areas of the body and avoid damaging non-target, healthy tissues. Both soft and stiff, bio-degradable and non-biodegradable nanoparticles are anticipated to be used to this end. It has been shown that stiff, non-biodegradable nanoparticles cause reactive oxygen species (ROS) generation and autophagy in a variety of cell lines in vitro. Both responses can lead to significant remodeling of the cytosol and even apoptosis. Thus these are crucial cellular functions to understand. Improved assays have uncovered crucial roles of the Akt/mTOR signaling pathway in both ROS generation and autophagy initiation after cells have internalized stiff, non-biodegradable nanoparticles over varying geometries in culture. Of particular – yet unresolved – interest is how these nanoparticles cause the activation of these pathways. This article reviews the most recent advances in nanoparticle generation of ROS and autophagy initiation with a focus on stiff, non-biodegradable technologies. We provide experimental guidelines to the reader for fleshing out the effects of their nanoparticles on the above pathways with the goal of tuning nanoparticle design.
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.01.001
      Issue No: Vol. 122 (2017)
       
  • Macrophage-based therapeutic strategies in regenerative medicine
    • Authors: Kara L. Spiller; Timothy J. Koh
      Pages: 74 - 83
      Abstract: Publication date: 1 December 2017
      Source:Advanced Drug Delivery Reviews, Volume 122
      Author(s): Kara L. Spiller, Timothy J. Koh
      Mounting evidence suggests that therapeutic cell and drug delivery strategies designed to actively harness the regenerative potential of the inflammatory response have great potential in regenerative medicine. In particular, macrophages have emerged as a primary target because of their critical roles in regulating multiple phases of tissue repair through their unique ability to rapidly shift phenotypes. Herein, we review macrophage-based therapies, focusing on the translational potential for cell delivery of ex vivo-activated macrophages and delivery of molecules and biomaterials to modulate accumulation and phenotype of endogenous macrophages. We also review current obstacles to progress in translating basic findings to therapeutic applications, including the need for improved understanding of context-dependent macrophage functions and the myriad factors that regulate macrophage phenotype; potential species-specific differences (e.g. humans versus mice); quality control issues; and the lack of standardized procedures and nomenclature for characterizing macrophages. Looking forward, the inherent plasticity of macrophages represents a daunting challenge for harnessing these cells in regenerative medicine therapies but also great opportunity for improving patient outcomes in a variety of pathological conditions.
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.05.010
      Issue No: Vol. 122 (2017)
       
  • Mimicking oxygen delivery and waste removal functions of blood
    • Authors: Huaifa Zhang; Jake E. Barralet
      Pages: 84 - 104
      Abstract: Publication date: 1 December 2017
      Source:Advanced Drug Delivery Reviews, Volume 122
      Author(s): Huaifa Zhang, Jake E. Barralet
      In addition to immunological and wound healing cell and platelet delivery, ion stasis and nutrient supply, blood delivers oxygen to cells and tissues and removes metabolic wastes. For decades researchers have been trying to develop approaches that mimic these two immediately vital functions of blood. Oxygen is crucial for the long-term survival of tissues and cells in vertebrates. Hypoxia (oxygen deficiency) and even at times anoxia (absence of oxygen) can occur during organ preservation, organ and cell transplantation, wound healing, in tumors and engineering of tissues. Different approaches have been developed to deliver oxygen to tissues and cells, including hyperbaric oxygen therapy (HBOT), normobaric hyperoxia therapy (NBOT), using biochemical reactions and electrolysis, employing liquids with high oxygen solubility, administering hemoglobin, myoglobin and red blood cells (RBCs), introducing oxygen-generating agents, using oxygen-carrying microparticles, persufflation, and peritoneal oxygenation. Metabolic waste accumulation is another issue in biological systems when blood flow is insufficient. Metabolic wastes change the microenvironment of cells and tissues, influence the metabolic activities of cells, and ultimately cause cell death. This review examines advances in blood mimicking systems in the field of biomedical engineering in terms of oxygen delivery and metabolic waste removal.
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.02.001
      Issue No: Vol. 122 (2017)
       
  • Stem cell therapy clinical research: A regulatory conundrum for academia
    • Authors: Anjali Nagpal; Chris Juttner; Monica Anne Hamilton-Bruce; Paul Rolan; Simon A. Koblar
      Pages: 105 - 114
      Abstract: Publication date: 1 December 2017
      Source:Advanced Drug Delivery Reviews, Volume 122
      Author(s): Anjali Nagpal, Chris Juttner, Monica Anne Hamilton-Bruce, Paul Rolan, Simon A. Koblar
      The encouraging pace of discovery and development in the field of regenerative medicine holds tremendous potential for bringing therapies to the clinic that may offer meaningful benefit to patients, particularly in diseases with no or suboptimal therapeutic options. Academic researchers will continue to play a critical role in developing concepts and therapies, thus determining whether regenerative medicine will be able to live up to this potential that clearly excites clinicians, researchers and patients alike. This review summarises recent developments in regulatory frameworks across different countries that aim to ensure adequate oversight of the development of regenerative medicine products, which are unique in structural and functional complexity when compared to traditional chemical drugs and fully characterised biological drugs. It discusses the implications of these developments for researchers aiming to make the challenging transition from laboratory to clinical development of these therapies and considers possible pragmatic solutions that could accelerate this process that is essential to maintain research credibility and ensure patient safety.
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2016.10.001
      Issue No: Vol. 122 (2017)
       
  • Fibroblasts and extracellular matrix: Targeting and therapeutic tools in
           fibrosis and cancer
    • Authors: Jai Prakash; Massimo Pinzani
      Pages: 1 - 2
      Abstract: Publication date: 1 November 2017
      Source:Advanced Drug Delivery Reviews, Volume 121
      Author(s): Jai Prakash, Massimo Pinzani


      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.11.008
      Issue No: Vol. 121 (2017)
       
  • Pathophysiology of liver fibrosis and the methodological barriers to the
           development of anti-fibrogenic agents
    • Authors: Katrin Böttcher; Massimo Pinzani
      Pages: 3 - 8
      Abstract: Publication date: 1 November 2017
      Source:Advanced Drug Delivery Reviews, Volume 121
      Author(s): Katrin Böttcher, Massimo Pinzani
      Liver fibrosis and cirrhosis resulting from long-standing liver damage represents a major health care burden worldwide. To date, there is no anti-fibrogenic agent available, making liver transplantation the only curative treatment for decompensated cirrhotic liver disease. Liver fibrosis can result from different underlying chronic liver disease, such as chronic viral infection, excessive alcohol consumption, fatty liver disease or autoimmune liver diseases. It is becoming increasingly recognised that as a result from different pathogenic mechanisms liver fibrosis must be considered as many different diseases for which individual treatment strategies need to be developed. Moreover, the pathogenic changes of both liver architecture and vascularisation in cirrhotic livers, as well as the lack of “true-to-life” in vitro models have impeded the development of an effective anti-fibrogenic drug. Thus, in order to identify an efficient anti-fibrogenic compound, novel in-vitro models mimicking the interplay between pro-fibrogenic cell populations, immune cells and, importantly, the extracellular matrix need to be developed.
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.05.016
      Issue No: Vol. 121 (2017)
       
  • Hepatic stellate cells as key target in liver fibrosis
    • Authors: Takaaki Higashi; Scott L. Friedman; Yujin Hoshida
      Pages: 27 - 42
      Abstract: Publication date: 1 November 2017
      Source:Advanced Drug Delivery Reviews, Volume 121
      Author(s): Takaaki Higashi, Scott L. Friedman, Yujin Hoshida
      Progressive liver fibrosis, induced by chronic viral and metabolic disorders, leads to more than one million deaths annually via development of cirrhosis, although no antifibrotic therapy has been approved to date. Transdifferentiation (or “activation”) of hepatic stellate cells is the major cellular source of matrix protein-secreting myofibroblasts, the major driver of liver fibrogenesis. Paracrine signals from injured epithelial cells, fibrotic tissue microenvironment, immune and systemic metabolic dysregulation, enteric dysbiosis, and hepatitis viral products can directly or indirectly induce stellate cell activation. Dysregulated intracellular signaling, epigenetic changes, and cellular stress response represent candidate targets to deactivate stellate cells by inducing reversion to inactivated state, cellular senescence, apoptosis, and/or clearance by immune cells. Cell type- and target-specific pharmacological intervention to therapeutically induce the deactivation will enable more effective and less toxic precision antifibrotic therapies.
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.05.007
      Issue No: Vol. 121 (2017)
       
  • The good and the bad collagens of fibrosis – Their role in signaling
           and organ function
    • Authors: M.A. Karsdal; S.H. Nielsen; D.J. Leeming; L.L. Langholm; M.J. Nielsen; T. Manon-Jensen; A. Siebuhr; N.S. Gudmann; S. Rønnow; J.M. Sand; S.J. Daniels; J.H. Mortensen; D. Schuppan
      Pages: 43 - 56
      Abstract: Publication date: 1 November 2017
      Source:Advanced Drug Delivery Reviews, Volume 121
      Author(s): M.A. Karsdal, S.H. Nielsen, D.J. Leeming, L.L. Langholm, M.J. Nielsen, T. Manon-Jensen, A. Siebuhr, N.S. Gudmann, S. Rønnow, J.M. Sand, S.J. Daniels, J.H. Mortensen, D. Schuppan
      Usually the dense extracellular structure in fibrotic tissues is described as extracellular matrix (ECM) or simply as collagen. However, fibrosis is not just fibrosis, which is already exemplified by the variant morphological characteristics of fibrosis due to viral versus cholestatic, autoimmune or toxic liver injury, with reticular, chicken wire and bridging fibrosis. Importantly, the overall composition of the ECM, especially the relative amounts of the many types of collagens, which represent the most abundant ECM molecules and which centrally modulate cellular functions and physiological processes, changes dramatically during fibrosis progression. We hypothesize that there are good and bad collagens in fibrosis and that a change of location alone may change the function from good to bad. Whereas basement membrane collagen type IV anchors epithelial and other cells in a polarized manner, the interstitial fibroblast collagens type I and III do not provide directional information. In addition, feedback loops from biologically active degradation products of some collagens are examples of the importance of having the right collagen at the right place and at the right time controlling cell function, proliferation, matrix production and fate. Examples are the interstitial collagen type VI and basement membrane collagen type XVIII. Their carboxyterminal propeptides serve as an adipose tissue hormone, endotrophin, and as a regulator of angiogenesis, endostatin, respectively. We provide an overview of the 28 known collagen types and propose that the molecular composition of the ECM in fibrosis needs careful attention to assess its impact on organ function and its potential to progress or reverse. Consequently, to adequately assess fibrosis and to design optimal antifibrotic therapies, we need to dissect the molecular entity of fibrosis for the molecular composition and spatial distribution of collagens and the associated ECM.
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.07.014
      Issue No: Vol. 121 (2017)
       
  • Therapeutic pro-fibrogenic signaling pathways in fibroblasts
    • Authors: Stefania Cannito; Erica Novo; Maurizio Parola
      Pages: 57 - 84
      Abstract: Publication date: 1 November 2017
      Source:Advanced Drug Delivery Reviews, Volume 121
      Author(s): Stefania Cannito, Erica Novo, Maurizio Parola
      Myofibroblasts (MFs) play a critical role in the progression of chronic inflammatory and fibroproliferative diseases in different tissues/organs, whatever the etiology. Fibrosis is preceded and sustained by persistent injury and inflammatory response in a profibrogenic scenario involving mutual interactions, operated by several mediators and pathways, of MFs and related precursor cells with innate immunity cells and virtually any cell type in a defined tissue. These interactions, mediators and related signaling pathways are critical in initiating and perpetuating the differentiation of precursor cells into MFs that in different tissues share peculiar traits and phenotypic responses, including the ability to proliferate, produce ECM components, migrate and contribute to the modulation of inflammatory response and tissue angiogenesis. Literature studies related to liver, lung and kidney fibrosis have outlined a number of MF-related core regulatory fibrogenic signaling pathways conserved across these different organs and potentially targetable in order to develop effective antifibrotic therapeutic strategies.
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.05.017
      Issue No: Vol. 121 (2017)
       
  • Effects of Klotho on fibrosis and cancer: A renal focus on mechanisms and
           therapeutic strategies
    • Authors: Rik Mencke; Hannes Olauson; Jan-Luuk Hillebrands
      Pages: 85 - 100
      Abstract: Publication date: 1 November 2017
      Source:Advanced Drug Delivery Reviews, Volume 121
      Author(s): Rik Mencke, Hannes Olauson, Jan-Luuk Hillebrands
      Klotho is a membrane-bound protein predominantly expressed in the kidney, where it acts as a permissive co-receptor for Fibroblast Growth Factor 23. In its shed form, Klotho exerts anti-fibrotic effects in several tissues. Klotho-deficient mice spontaneously develop fibrosis and Klotho deficiency exacerbates the disease progression in fibrotic animal models. Furthermore, Klotho overexpression or supplementation protects against fibrosis in various models of renal and cardiac fibrotic disease. These effects are mediated at least partially by the direct inhibitory effects of soluble Klotho on TGFβ1 signaling, Wnt signaling, and FGF2 signaling. Soluble Klotho, as present in the circulation, appears to be the primary mediator of anti-fibrotic effects. Similarly, through inhibition of the TGFβ1, Wnt, FGF2, and IGF1 signaling pathways, Klotho also inhibits tumorigenesis. The Klotho promoter gene is generally hypermethylated in cancer, and overexpression or supplementation of Klotho has been found to inhibit tumor growth in various animal models. This review focuses on the protective effects of soluble Klotho in inhibiting renal fibrosis and fibrosis in distant organs secondary to renal Klotho deficiency. We also discuss the structure-function relationships of Klotho domains and biological effects in the context of potential targeted treatment strategies.
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.07.009
      Issue No: Vol. 121 (2017)
       
  • Drug targeting to myofibroblasts: Implications for fibrosis and cancer
    • Authors: Saleh Yazdani; Ruchi Bansal; Jai Prakash
      Pages: 101 - 116
      Abstract: Publication date: 1 November 2017
      Source:Advanced Drug Delivery Reviews, Volume 121
      Author(s): Saleh Yazdani, Ruchi Bansal, Jai Prakash
      Myofibroblasts are the key players in extracellular matrix remodeling, a core phenomenon in numerous devastating fibrotic diseases. Not only in organ fibrosis, but also the pivotal role of myofibroblasts in tumor progression, invasion and metastasis has recently been highlighted. Myofibroblast targeting has gained tremendous attention in order to inhibit the progression of incurable fibrotic diseases, or to limit the myofibroblast-induced tumor progression and metastasis. In this review, we outline the origin of myofibroblasts, their general characteristics and functions during fibrosis progression in three major organs: liver, kidneys and lungs as well as in cancer. We will then discuss the state-of-the art drug targeting technologies to myofibroblasts in context of the above-mentioned organs and tumor microenvironment. The overall objective of this review is therefore to advance our understanding in drug targeting to myofibroblasts, and concurrently identify opportunities and challenges for designing new strategies to develop novel diagnostics and therapeutics against fibrosis and cancer.
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.07.010
      Issue No: Vol. 121 (2017)
       
  • 3D in vitro models of liver fibrosis
    • Authors: Leo A. van Grunsven
      Pages: 133 - 146
      Abstract: Publication date: 1 November 2017
      Source:Advanced Drug Delivery Reviews, Volume 121
      Author(s): Leo A. van Grunsven
      Animal testing is still the most popular preclinical assessment model for liver fibrosis. To develop efficient anti-fibrotic therapies, robust and representative in vitro models are urgently needed. The most widely used in vitro fibrosis model is the culture-induced activation of primary rodent hepatic stellate cells. While these cultures have contributed greatly to the current understanding of hepatic stellate cell activation, they seem to be inadequate to cover the complexity of this regenerative response. This review summarizes recent progress towards the development of 3D culture models of liver fibrosis. Thus far, only a few hepatic culture systems have successfully implemented hepatic stellate cells (or other non-parenchymal cells) into hepatocyte cultures. Recent advances in bioprinting, spheroid- and precision-cut liver slice cultures and the use of microfluidic bioreactors will surely lead to valid 3D in vitro models of liver fibrosis in the near future.
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.07.004
      Issue No: Vol. 121 (2017)
       
  • Engineering in vitro models of hepatofibrogenesis
    • Authors: Giuseppe Mazza; Walid Al-Akkad; Krista Rombouts
      Pages: 147 - 157
      Abstract: Publication date: 1 November 2017
      Source:Advanced Drug Delivery Reviews, Volume 121
      Author(s): Giuseppe Mazza, Walid Al-Akkad, Krista Rombouts
      Chronic liver disease is a major cause of morbidity and mortality worldwide marked by chronic inflammation and fibrosis/scarring, resulting in end-stage liver disease and its complications. Hepatic stellate cells (HSCs) are a dominant contributor to liver fibrosis by producing excessive extracellular matrix (ECM), irrespective of the underlying disease aetiologies, and for many decades research has focused on the development of a number of anti-fibrotic strategies targeting this cell. Despite major improvements in two-dimensional systems (2D) by using a variety of cell culture models of different complexity, an efficient anti-fibrogenic therapy has yet to be developed. The development of well-defined three-dimensional (3D) in vitro models, which mimic ECM structures as found in vivo, have demonstrated the importance of cell-matrix bio-mechanics, the complex interactions between HSCs and hepatocytes and other non-parenchymal cells, and this to improve and promote liver cell-specific functions. Henceforth, refinement of these 3D in vitro models, which reproduce the liver microenvironment, will lead to new objectives and to a possible new era in the search for antifibrogenic compounds.
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.05.018
      Issue No: Vol. 121 (2017)
       
  • The enigma of stem cell-based therapies – how to conquer the death
           valley of therapy development
    • Authors: Gustav Steinhoff
      First page: 1
      Abstract: Publication date: 1 October 2017
      Source:Advanced Drug Delivery Reviews, Volume 120
      Author(s): Gustav Steinhoff


      PubDate: 2017-11-26T02:18:38Z
      DOI: 10.1016/j.addr.2017.11.006
      Issue No: Vol. 120 (2017)
       
  • Strategies to develop endogenous stem cell-recruiting bioactive materials
           for tissue repair and regeneration
    • Authors: Settimio Pacelli; Sayantani Basu; Jonathan Whitlow; Aparna Chakravarti; Francisca Acosta; Arushi Varshney; Saman Modaresi; Cory Berkland; Arghya Paul
      Pages: 50 - 70
      Abstract: Publication date: 1 October 2017
      Source:Advanced Drug Delivery Reviews, Volume 120
      Author(s): Settimio Pacelli, Sayantani Basu, Jonathan Whitlow, Aparna Chakravarti, Francisca Acosta, Arushi Varshney, Saman Modaresi, Cory Berkland, Arghya Paul
      A leading strategy in tissue engineering is the design of biomimetic scaffolds that stimulate the body's repair mechanisms through the recruitment of endogenous stem cells to sites of injury. Approaches that employ the use of chemoattractant gradients to guide tissue regeneration without external cell sources are favored over traditional cell-based therapies that have limited potential for clinical translation. Following this concept, bioactive scaffolds can be engineered to provide a temporally and spatially controlled release of biological cues, with the possibility to mimic the complex signaling patterns of endogenous tissue regeneration. Another effective way to regulate stem cell activity is to leverage the inherent chemotactic properties of extracellular matrix (ECM)-based materials to build versatile cell-instructive platforms. This review introduces the concept of endogenous stem cell recruitment, and provides a comprehensive overview of the strategies available to achieve effective cardiovascular and bone tissue regeneration.
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      PubDate: 2017-11-26T02:18:38Z
      DOI: 10.1016/j.addr.2017.07.011
      Issue No: Vol. 120 (2017)
       
  • Molecular imaging in stem cell-based therapies of cardiac diseases
    • Authors: Xiang Li; Marcus Hacker
      Pages: 71 - 88
      Abstract: Publication date: 1 October 2017
      Source:Advanced Drug Delivery Reviews, Volume 120
      Author(s): Xiang Li, Marcus Hacker
      In the past 15years, despite that regenerative medicine has shown great potential for cardiovascular diseases, the outcome and safety of stem cell transplantation has shown controversial results in the published literature. Medical imaging might be useful for monitoring and quantifying transplanted cells within the heart and to serially characterize the effects of stem cell therapy of the myocardium. From the multiple available noninvasive imaging techniques, magnetic resonance imaging and nuclear imaging by positron (PET) or single photon emission computer tomography (SPECT) are the most used clinical approaches to follow the fate of transplanted stem cells in vivo. In this article, we provide a review on the role of different noninvasive imaging modalities and discuss their advantages and disadvantages. We focus on the different in-vivo labeling and reporter gene imaging strategies for stem cell tracking as well as the concept and reliability to use imaging parameters as noninvasive surrogate endpoints for the evaluation of the post-therapeutic outcome.
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      PubDate: 2017-11-26T02:18:38Z
      DOI: 10.1016/j.addr.2017.07.012
      Issue No: Vol. 120 (2017)
       
  • Advances in cancer stem cell targeting: How to strike the evil at its root
    • Authors: Brigitte M. Pützer; Manish Solanki; Ottmar Herchenröder
      Pages: 89 - 107
      Abstract: Publication date: 1 October 2017
      Source:Advanced Drug Delivery Reviews, Volume 120
      Author(s): Brigitte M. Pützer, Manish Solanki, Ottmar Herchenröder
      Cancer progression to metastatic stages is still unmanageable and the promise of effective anti-metastatic therapy remains largely unmet, emphasizing the need to develop novel therapeutics. The special focus here is on cancer stem cells (CSC) as the seed of tumor initiation, epithelial-mesenchymal transition, chemoresistance and, as a consequence, drivers of metastatic dissemination. We report on targeted therapies gearing towards the CSC's internal and membrane-anchored markers using agents such as antibody derivatives, nucleic therapeutics, small molecules and genetic payloads. Another emphasis lies on novel proceedings envisaged to deliver current and prospective therapies to the target sites using newest viral and non-viral vector technologies. In this review, we summarize recent progress and remaining challenges in therapeutic strategies to combat CSC.
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      PubDate: 2017-11-26T02:18:38Z
      DOI: 10.1016/j.addr.2017.07.013
      Issue No: Vol. 120 (2017)
       
  • Gene regulation in adult neural stem cells. Current challenges and
           possible applications
    • Authors: Juan Manuel Encinas; Carlos P. Fitzsimons
      Pages: 118 - 132
      Abstract: Publication date: 1 October 2017
      Source:Advanced Drug Delivery Reviews, Volume 120
      Author(s): Juan Manuel Encinas, Carlos P. Fitzsimons
      Adult neural stem and progenitor cells (NSPCs) offer a unique opportunity for neural regeneration and niche modification in physiopathological conditions, harnessing the capability to modify from neuronal circuits to glial scar. Findings exposing the vast plasticity and potential of NSPCs have accumulated over the past years and we currently know that adult NSPCs can naturally give rise not only to neurons but also to astrocytes and reactive astrocytes, and eventually to oligodendrocytes through genetic manipulation. We can consider NSPCs as endogenous flexible tools to fight against neurodegenerative and neurological disorders and aging. In addition, NSPCs can be considered as active agents contributing to chronic brain alterations and as relevant cell populations to be preserved, so that their main function, neurogenesis, is not lost in damage or disease. Altogether we believe that learning to manipulate NSPC is essential to prevent, ameliorate or restore some of the cognitive deficits associated with brain disease and injury, and therefore should be considered as target for future therapeutic strategies. The first step to accomplish this goal is to target them specifically, by unveiling and understanding their unique markers and signaling pathways.
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      PubDate: 2017-11-26T02:18:38Z
      DOI: 10.1016/j.addr.2017.07.016
      Issue No: Vol. 120 (2017)
       
  • Drug delivery and tissue engineering to promote wound healing in the
           Immunocompromised host: Current challenges and future directions
    • Authors: Alexander M. Tatara; Dimitrios P. Kontoyiannis; Antonios G. Mikos
      Abstract: Publication date: Available online 6 December 2017
      Source:Advanced Drug Delivery Reviews
      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: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.12.001
       
  • The state-of-play and future of antibody therapeutics
    • Authors: Zehra Elgundi; Mouhamad Reslan Esteban Cruz Vicki Sifniotis Veysel Kayser
      Abstract: Publication date: 1 December 2017
      Source:Advanced Drug Delivery Reviews, Volume 122
      Author(s): Zehra Elgundi, Mouhamad Reslan, Esteban Cruz, Vicki Sifniotis, Veysel Kayser
      It has been over four decades since the development of monoclonal antibodies (mAbs) using a hybridoma cell line was first reported. Since then more than thirty therapeutic antibodies have been marketed, mostly as oncology, autoimmune and inflammatory therapeutics. While antibodies are very efficient, their cost-effectiveness has always been discussed owing to their high costs, accumulating to more than one billion dollars from preclinical development through to market approval. Because of this, therapeutic antibodies are inaccessible to some patients in both developed and developing countries. The growing interest in biosimilar antibodies as affordable versions of therapeutic antibodies may provide alternative treatment options as well potentially decreasing costs. As certain markets begin to capitalize on this opportunity, regulatory authorities continue to refine the requirements for demonstrating quality, efficacy and safety of biosimilar compared to originator products. In addition to biosimilars, innovations in antibody engineering are providing the opportunity to design biobetter antibodies with improved properties to maximize efficacy. Enhancing effector function, antibody drug conjugates (ADC) or targeting multiple disease pathways via multi-specific antibodies are being explored. The manufacturing process of antibodies is also moving forward with advancements relating to host cell production and purification processes. Studies into the physical and chemical degradation pathways of antibodies are contributing to the design of more stable proteins guided by computational tools. Moreover, the delivery and pharmacokinetics of antibody-based therapeutics are improving as optimized formulations are pursued through the implementation of recent innovations in the field.
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      PubDate: 2017-12-07T06:23:10Z
       
  • Pulmonary drug delivery to older people
    • Authors: Martin Wallin; Tatsuaki Tagami; Lan Chen; Mingshi Yang; Hak-Kim Chan
      Abstract: Publication date: Available online 29 November 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Martin Wallin, Tatsuaki Tagami, Lan Chen, Mingshi Yang, Hak-Kim Chan
      Pulmonary diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are common in older people. Treatment principles are well established in this group of patients; however, inadequate training and improper inhaler techniques often results in poor treatment outcomes. Healthcare professionals often do not have the required knowledge about the most common inhaler devices. Age-related conditions like cognitive ability and physical strength would also impact on the inhaler usage. Pharmacokinetics and pharmacodynamics may be affected by physiological changes, like impaired renal and hepatic functions and reduced lung functions. Adjusting and optimizing the inhaler device to the patient preferences, improvement of the drug formulation and inhalers, and using different adherence strategies might improve the treatment outcomes in elderly patients.
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.11.010
       
  • Bench-to-bedside translation of dendrimers: Reality or utopia' A
           concise analysis
    • Authors: Serge Mignani; João Rodrigues; Helena Tomas; René Roy; Xiangyang Shi; Jean-Pierre Majoral
      Abstract: Publication date: Available online 16 November 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Serge Mignani, João Rodrigues, Helena Tomas, René Roy, Xiangyang Shi, Jean-Pierre Majoral
      Nanomedicine, which is an application of nanotechnologies in healthcare is developed to improve the treatments and lives of patients suffering from a range of disorders and to increase the successes of drug candidates. Within the nanotechnology universe, the remarkable unique and tunable properties of dendrimers have made them promising tools for diverse biomedical applications such as drug delivery, gene therapy and diagnostic. Up-to-date, very few dendrimers has yet gained regulatory approval for systemic administration, why? In this critical review, we briefly focus on the list of desired basic dendrimer requirements for decision-making purpose by the scientists (go/no-go decision), in early development stages, to become clinical candidates, and to move towards Investigational New Drugs (IND) application submission. In addition, the successful translation between research and clinic should be performed by the implementation of a simple roadmap to jump the ‘valley of death’ successfully.
      Graphical abstract image

      PubDate: 2017-11-26T02:18:38Z
      DOI: 10.1016/j.addr.2017.11.007
       
  • Fibrosis imaging: Current concepts and future directions
    • Authors: Maike Baues; Anshuman Dasgupta; Josef Ehling; Jai Prakash; Peter Boor; Frank Tacke; Fabian Kiessling; Twan Lammers
      Abstract: Publication date: Available online 3 November 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Maike Baues, Anshuman Dasgupta, Josef Ehling, Jai Prakash, Peter Boor, Frank Tacke, Fabian Kiessling, Twan Lammers
      Fibrosis plays an important role in many different pathologies. It results from tissue injury, chronic inflammation, autoimmune reactions and genetic alterations, and it is characterized by the excessive deposition of extracellular matrix components. Biopsies are routinely employed for fibrosis diagnosis, but they suffer from several drawbacks, including their invasive nature, sampling variability and limited spatial information. To overcome these limitations, multiple different imaging tools and technologies have been evaluated over the years, including X-ray imaging, computed tomography (CT), ultrasound (US), magnetic resonance imaging (MRI), positron emission tomography (PET) and single-photon emission computed tomography (SPECT). These modalities can provide anatomical, functional and molecular imaging information which is useful for fibrosis diagnosis and staging, and they may also hold potential for the longitudinal assessment of therapy responses. Here, we summarize the use of non-invasive imaging techniques for monitoring fibrosis in systemic autoimmune diseases, in parenchymal organs (such as liver, kidney, lung and heart), and in desmoplastic cancers. We also discuss how imaging biomarkers can be integrated in (pre-) clinical research to individualize and improve anti-fibrotic therapies.
      Graphical abstract image

      PubDate: 2017-11-26T02:18:38Z
      DOI: 10.1016/j.addr.2017.10.013
       
  • Injectable Network Biomaterials via Molecular or Colloidal Self-Assembly
    • Authors: Jugal Kishore Sahoo; Michael A. VandenBerg; Matthew J. Webber
      Abstract: Publication date: Available online 10 November 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Jugal Kishore Sahoo, Michael A. VandenBerg, Matthew J. Webber
      Self-assembly is a powerful tool to create functional materials. A specific application for which self-assembled materials are ideally suited is in creating injectable biomaterials. Contrasting with traditional biomaterials that are implanted through surgical means, injecting biomaterials through the skin offers numerous advantages, expanding the scope and impact for biomaterials in medicine. In particular, self-assembled biomaterials prepared from molecular or colloidal interactions have been frequently explored. The strategies to create these materials are varied, taking advantage of engineered oligopeptides, proteins, and nanoparticles as well as affinity-mediated crosslinking of synthetic precursors. Self-assembled materials typically facilitate injectability through two different mechanisms: i) in situ self-assembly, whereby materials would be administered in a monomeric or oligomeric form and self-assemble in response to some physiologic stimulus, or ii) self-assembled materials that, by virtue of their dynamic, non-covalent interactions, shear-thin and self-heal to facilitate flow within a syringe and subsequent reassembly of material form at the injection site. Indeed, many classes of materials are capable of being injected using a combination of these two mechanisms. Particular utility has been noted for self-assembled biomaterials in the context of tissue engineering, regenerative medicine, drug delivery, and immunoengineering. Given the controlled and multifunctional nature of many self-assembled materials demonstrated to date, we project a future where injectable self-assembled biomaterials afford improved practice in advancing healthcare.
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      PubDate: 2017-11-16T12:01:25Z
      DOI: 10.1016/j.addr.2017.11.005
       
  • Transflammation: Innate immune signaling in nuclear reprogramming
    • Authors: Shu Meng; Palas Chanda; Rajarajan A. Thandavarayan; John P. Cooke
      Abstract: Publication date: Available online 13 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Shu Meng, Palas Chanda, Rajarajan A. Thandavarayan, John P. Cooke
      Induction of pluripotency in somatic cells by retroviral overexpression of four transcription factors has revolutionized the field of stem cell biology and regenerative medicine. The efficient induction of pluripotency requires the activation of innate immune signaling in a process termed “transflammation” (Lee et al., 2012). Specifically, the stimulation of pattern recognition receptors (PRRs) causes global alterations in the expression and activity of epigenetic modifiers to favor an open chromatin configuration. Activation of toll-like receptors (TLR) or RIG-1-like receptors (RLR) (Sayed et al. 2017) trigger signaling cascades that result in NFκB or IRF-3 mediated changes in epigenetic plasticity that facilitate reprogramming. Another form of nuclear reprogramming is so-called direct reprogramming or transdifferentiation of one somatic cell to another lineage. We have shown that transdifferentiation of human fibroblasts to endothelial cells also involves transflammation (Sayed et al., 2015). Recently, we also identified reactive oxygen species (ROS) (Zhou et al. 2016) and reactive nitrogen species (RNS) (Meng et al., 2016) as mediators of innate immune signaling in nuclear reprogramming. Innate immune signaling plays a key role in nuclear reprogramming by regulating DNA accessibility (Fig. 1). Here, we review recent progress of innate immunity signaling in nuclear reprogramming and epigenetic plasticity.
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      PubDate: 2017-11-16T12:01:25Z
      DOI: 10.1016/j.addr.2017.09.010
       
  • MEMS devices for drug delivery
    • Authors: Hyunjoo J. Lee; Nakwon Choi; Eui-Sung Yoon; Il-Joo Cho
      Abstract: Publication date: Available online 5 November 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Hyunjoo J. Lee, Nakwon Choi, Eui-Sung Yoon, Il-Joo Cho
      Novel drug delivery systems based on microtechnology have advanced tremendously, but yet face some technological and societal hurdles to fully achieve their potential. The novel drug delivery systems aim to deliver drugs in a spatiotemporal- and dosage-controlled manner with a goal to address the unmet medical needs from oral delivery and hypodermic injection. The unmet needs include effective delivery of new types of drug candidates that are otherwise insoluble and unstable, targeted delivery to areas protected by barriers (e.g. brain and posterior eye segment), localized delivery of potent drugs, and improved patient compliance. After scrutinizing the design considerations and challenges associated with delivery to areas that cannot be efficiently targeted through standard drug delivery (e.g. brain, posterior eye segment, and gastrointestinal tract), this review provides a summary of recent advances that addressed these challenges and summarizes yet unresolved problems in each target area. The opportunities for innovation in devising the novel drug delivery systems are still high; with integration of advanced microtechnology, advanced fabrication of biomaterials, and biotechnology, the novel drug delivery is poised to be a promising alternative to the oral administration and hypodermic injection for a large spectrum of drug candidates.
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      PubDate: 2017-11-09T00:59:41Z
      DOI: 10.1016/j.addr.2017.11.003
       
  • The role of mucus as an invisible cloak to transepithelial drug delivery
           by nanoparticles
    • Authors: María García-Díaz; Ditlev Birch; Feng Wan; Hanne Mørck Nielsen
      Abstract: Publication date: Available online 5 November 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): María García-Díaz, Ditlev Birch, Feng Wan, Hanne Mørck Nielsen
      Mucosal administration of drugs and drug delivery systems has gained increasing interest. However, nanoparticles intended to protect and deliver drugs to epithelial surfaces require transport through the surface-lining mucus. Translation from bench to bedside is particularly challenging for mucosal administration since a variety of parameters will influence the specific barrier properties of the mucus including the luminal fluids, the microbiota, the mucus composition and clearance rate, and the condition of the underlying epithelia. Besides, after administration, nanoparticles interact with the mucosal components, forming a biomolecular corona that modulates their behavior and fate after mucosal administration. These interactions are greatly influenced by the nanoparticle properties and therefore different designs and surface-engineering strategies have been proposed. Overall, it is essential to evaluate these biomolecule-nanoparticle interactions by complementary techniques using complex and relevant mucus barrier matrices.
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      PubDate: 2017-11-09T00:59:41Z
      DOI: 10.1016/j.addr.2017.11.002
       
  • Mucus models to evaluate the diffusion of drugs and particles
    • Authors: Jaclyn Y. Lock; Taylor Carlson; Rebecca L. Carrier
      Abstract: Publication date: Available online 5 November 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Jaclyn Y. Lock, Taylor Carlson, Rebecca L. Carrier
      Mucus is a complex hydrogel that acts as a natural barrier to drug delivery at different mucosal surfaces including the respiratory, gastrointestinal, and vaginal tracts. To elucidate the role mucus plays in drug delivery, different in vitro, in vivo, and ex vivo mucus models and techniques have been utilized. Drug and drug carrier diffusion can be studied using various techniques in either isolated mucus gels or mucus present on cell cultures and tissues. The species, age, and potential disease state of the animal from which mucus is derived can all impact mucus composition and structure, and therefore impact drug and drug carrier diffusion. This review provides an overview of the techniques used to characterize drug and drug carrier diffusion, and discusses the advantages and disadvantages of the different models available to highlight the information they can afford.
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      PubDate: 2017-11-09T00:59:41Z
      DOI: 10.1016/j.addr.2017.11.001
       
  • Animal Models of Smoke Inhalation Injury and Related Acute and Chronic
           Lung Diseases
    • Authors: Katarzyna Reczyńska; Priyanka Tharkar; Sally Yunsun Kim; Yiwei Wang; Elzbieta Pamuła; Hak-Kim Chan; Wojciech Chrzanowski
      Abstract: Publication date: Available online 3 November 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Katarzyna Reczyńska, Priyanka Tharkar, Sally Yunsun Kim, Yiwei Wang, Elzbieta Pamuła, Hak-Kim Chan, Wojciech Chrzanowski
      Smoke inhalation injury leads to various acute and chronic lung diseases and thus is the dominant cause of fire-related fatalities. In a search for an effective treatment and validation of therapies different classes of animal models have been developed, which include both small and large animals. These models have advanced our understanding of the mechanism of smoke inhalation injury, enabling a better understanding of pathogenesis and pathophysiology and development of new therapies. However, none of the animal models fully mirrors human lungs and their pathologies. All animal models have their limitations in replicating complex clinical conditions associated with smoke inhalation injury in humans. Therefore, for a correct interpretation of the results and to avoid bias, a precise understanding of similarities and differences of lungs between different animal species and humans is critical. We have reviewed and presented comprehensive comparison of different animal models and their clinical relevance. We presented an overview of methods utilized to induce smoke inhalation injuries, airway micro−/ macrostructure, advantages and disadvantages of the most commonly used small and large animal models.
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      PubDate: 2017-11-09T00:59:41Z
      DOI: 10.1016/j.addr.2017.10.005
       
  • A slippery slope: On the origin, role and physiology of mucus
    • Authors: Farhan Taherali; Felipe Varum; Abdul W. Basit
      Abstract: Publication date: Available online 3 November 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Farhan Taherali, Felipe Varum, Abdul W. Basit
      The mucosa of the gastrointestinal tract, eyes, nose, lungs, cervix and vagina is lined by epithelium interspersed with mucus-secreting goblet cells, all of which contribute to their unique functions. This mucus provides an integral defence to the epithelium against noxious agents and pathogens. However, it can equally act as a barrier to drugs and delivery systems targeting epithelial passive and active transport mechanisms. This review highlights the various mucins expressed at different mucosal surfaces on the human body, and their role in creating a mucoid architecture to protect epithelia with specialized functions. Various factors compromising the barrier properties of mucus have been discussed, with an emphasis on how disease states and microbiota can alter the physical properties of mucus. For instance, Akkermansia muciniphila, a bacterium found in higher levels in the gut of lean individuals induces the production of a thickened gut mucus layer. The aims of this article are to elucidate the different physiological, biochemical and physical properties of bodily mucus, a keen appreciation of which will help circumvent the slippery slope of challenges faced in achieving effective mucosal drug and gene delivery.
      Graphical abstract image

      PubDate: 2017-11-09T00:59:41Z
      DOI: 10.1016/j.addr.2017.10.014
       
  • Stem Cells, Niches and Scaffolds: Applications to Burns and Wound Care
    • Authors: Suzanne M. Watt; Jonathan M. Pleat
      Abstract: Publication date: Available online 26 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Suzanne M. Watt, Jonathan M. Pleat
      The importance of skin to survival, and the devastating physical and psychological consequences of scarring following reparative healing of extensive or difficult to heal human wounds, cannot be disputed. We discuss the significant challenges faced by patients and healthcare providers alike in treating these wounds. New state of the art technologies have provided remarkable insights into the role of skin stem and progenitor cells and their niches in maintaining skin homeostasis and in reparative wound healing. Based on this knowledge, we examine different approaches to repair extensive burn injury and chronic wounds, including full and split thickness skin grafts, temporising matrices and scaffolds and composite cultured skin products. Notable developments include next generation skin substitutes to replace split thickness skin autografts and next generation gene editing coupled with cell therapies to treat genodermatoses. Further refinements are predicted with the advent of bioprinting technologies, and newly defined biomaterials and autologous cell sources that can be engineered to more accurately replicate human skin architecture, function and cosmesis. These advances will undoubtedly improve quality of life for patients with extensive burns and difficult to heal wounds.
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      PubDate: 2017-11-02T00:40:33Z
      DOI: 10.1016/j.addr.2017.10.012
       
  • The role of mucus on drug transport and its potential to affect
           therapeutic outcomes
    • Authors: Xabier Murgia; Brigitta Loretz; Olga Hartwig; Marius Hittinger; Claus-Michael Lehr
      Abstract: Publication date: Available online 26 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Xabier Murgia, Brigitta Loretz, Olga Hartwig, Marius Hittinger, Claus-Michael Lehr
      A layer of mucus covers the surface of all wet epithelia throughout the human body. Mucus is a hydrogel mainly composed of water, mucins (glycoproteins), DNA, proteins, lipids, and cell debris. This complex composition yields a tenacious viscoelastic hydrogel that lubricates and protects the exposed epithelia from external threats and enzymatic degradation. The natural protective role of mucus is nowadays acknowledged as a major barrier to be overcome in non-invasive drug delivery. The heterogeneity of mucus components offers a wide range of potential chemical interaction sites for macromolecules, while the mesh-like architecture given to mucus by the intermolecular cross-linking of mucin molecules results in a dense network that physically, and in a size-dependent manner, hinders the diffusion of nanoparticles through mucus. Consequently, drug diffusion, epithelial absorption, drug bioavailability, and ultimately therapeutic outcomes of mucosal drug delivery can be attenuated.
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      PubDate: 2017-11-02T00:40:33Z
      DOI: 10.1016/j.addr.2017.10.009
       
  • Epigenetic reprogramming in liver fibrosis and cancer
    • Authors: Caroline L. Wilson; Derek A. Mann; Lee A. Borthwick
      Abstract: Publication date: Available online 25 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Caroline L. Wilson, Derek A. Mann, Lee A. Borthwick
      Novel insights into the epigenetic control of chronic liver diseases are now emerging. Recent advances in our understanding of the critical roles of DNA methylation, histone modifications and ncRNA may now be exploited to improve management of fibrosis/cirrhosis and cancer. Furthermore, improved technologies for the detection of epigenetic markers from patients' blood and tissues will vastly improve diagnosis, treatment options and prognostic tracking. The aim of this review is to present recent findings from the field of liver epigenetics and to explore their potential for translation into therapeutics to prevent disease promoting epigenome reprogramming and reverse epigenetic changes.
      Graphical abstract image

      PubDate: 2017-10-26T01:44:14Z
      DOI: 10.1016/j.addr.2017.10.011
       
  • Enzyme decorated drug carriers: Targeted swords to cleave and overcome the
           mucus barrier
    • Authors: Claudia Menzel; Andreas Bernkop-Schnürch
      Abstract: Publication date: Available online 24 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Claudia Menzel, Andreas Bernkop-Schnürch
      The use of mucus permeating drug carrier systems being able to overcome the mucus barrier can lead to a remarkable enhancement in bioavailability. One promising approach is the design of mucolytic enzyme decorated carrier systems (MECS). These systems include micro- and nanoparticles as well as self-emulsifying drug delivery systems (SEDDS) decorated with mucin cleaving enzymes such as papain (PAP) or bromelain (BRO). MECS are able to cross the mucus barrier in a comparatively efficient manner by cleaving mucus substructures in front of them on their way to the epithelium. Thereby these enzymes hydrolyze peptide bonds of mucus glycoproteins forming tiny holes or passages through the mucus. In various in vitro and in vivo studies MECS proved to be superior in their mucus permeating properties over nanocarriers without enzyme decoration. PAP decorated nanoparticles, for instance, remained 3h after oral administration to an even 2.5-fold higher extend in rat small intestine than the corresponding undecorated nanoparticles permeating the intestinal mucus gel layer to a much lower degree. As MECS break up the mucus network only locally without destroying its overall protective barrier function, even long term treatments with such systems seem feasible. Within this review article we address different drug carrier systems decorated with various types of enzymes, their particular pros and cons and potential applications.
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      PubDate: 2017-10-26T01:44:14Z
      DOI: 10.1016/j.addr.2017.10.004
       
  • Restoration of skin pigmentation after deep partial or full-thickness burn
           injury
    • Authors: Niann-Tzyy Dai; Hsin-I Chang; Yi-Wen Wang; Keng-Yen Fu; Tai-Chun Huang; Nien-Chi Huang; Jhen-Kai Li; Pai-Shan Hsieh; Lien-Guo Dai; Chao-Kuei Hsu; Peter K. Maitz
      Abstract: Publication date: Available online 24 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Niann-Tzyy Dai, Hsin-I Chang, Yi-Wen Wang, Keng-Yen Fu, Tai-Chun Huang, Nien-Chi Huang, Jhen-Kai Li, Pai-Shan Hsieh, Lien-Guo Dai, Chao-Kuei Hsu, Peter K. Maitz
      Significant skin pigmentation changes occur when patients suffer deep burn injuries. These pigmentation disorders may cause not only cosmetic and psychological issues, but more importantly it increases the risk of skin cancer or photoaging. Severe burns significantly effect on the process of repigmentation as the pigmentation is tightly regulated by cell proliferation and differentiation of melanocytes and melanocyte stem cells which are housing in the epidermis and hair follicles of the skin. In the present review, we discuss the possible mechanisms to replenish the melanocytes from the healthy epidermis and hair follicles surrounding burn wounds. The molecular mechanisms of skin repigmentation following healing of burn injuries includes the differentiation of melanoblasts into melanocytes, the distribution and responses of melanocytes and melanocyte stem cells after burn injury, and the regulation of melanin production. We also reviewed advanced therapeutic strategies to treat pigmentation disorders, such as convectional surgery, laser, UV treatment and emerging concepts in skin tissue-engineering.
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      PubDate: 2017-10-26T01:44:14Z
      DOI: 10.1016/j.addr.2017.10.010
       
  • Insights into the key roles of epigenetics in matrix
           macromolecules-associated wound healing
    • Authors: Zoi Piperigkou; Martin Götte; Achilleas D. Theocharis; Nikos K. Karamanos
      Abstract: Publication date: Available online 24 October 2017
      Source:Advanced Drug Delivery Reviews
      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: 2017-10-26T01:44:14Z
      DOI: 10.1016/j.addr.2017.10.008
       
  • Stem cells and heart disease - brake or accelerator'
    • Authors: Gustav Steinhoff; Julia Nesteruk; Markus Wolfien; Jana Große; Ulrike Ruch; Praveen Vasudevan; Paula Müller
      Abstract: Publication date: Available online 18 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Gustav Steinhoff, Julia Nesteruk, Markus Wolfien, Jana Große, Ulrike Ruch, Praveen Vasudevan, Paula Müller
      After two decades of intensive research and attempts of clinical translation, stem cell based therapies for cardiac diseases are not getting closer to clinical success. This review tries to unravel the obstacles and focuses on underlying mechanisms as the target for regenerative therapies. At present, the principal outcome in clinical therapy does not reflect experimental evidence. It seems that the scientific obstacle is a lack of integration of knowledge from tissue repair and disease mechanisms. Recent insights from clinical trials delineate mechanisms of stem cell dysfunction and gene defects in repair mechanisms as cause of atherosclerosis and heart disease. These findings require a redirection of current practice of stem cell therapy and a reset using more detailed analysis of stem cell function interfering with disease mechanisms. To accelerate scientific development the authors suggest intensifying unified computational data analysis and shared data knowledge by using open-access data platforms
      Graphical abstract image

      PubDate: 2017-10-26T01:44:14Z
      DOI: 10.1016/j.addr.2017.10.007
       
  • The application of mesenchymal stem cells to treat thermal and radiation
           burns
    • Authors: Kathleen Rodgers; Sachin S. Jadhav
      Abstract: Publication date: Available online 12 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Kathleen Rodgers, Sachin S. Jadhav
      Mesenchymal stem cells (MSCs) have been developed for a number of indications due to their regenerative and anti-inflammatory phenotypes and their utility is enhanced by the fact that allogeneic transplant is feasible with this cell type. Animal studies and early human cases indicate that this has the potential to be an exciting new therapy for treating chronic non-healing wounds such as diabetic ulcers, burns and cutaneous radiation burns. This review will focus on the use of MSCs to treat thermal and radiation burns. Large, severe burns are difficult to treat and pose a major public health burden worldwide. They are characterized by an extensive loss of the outer protective barrier, delayed wound healing, increased oxidative stress and a heightened inflammatory state. The breakdown of the protective barrier results in increased susceptibility to fluid loss and bacterial sepsis. In the case of radiation burns, chronic inflammation can result in subsequent waves of tissue injury leading to skin breakdown and necrosis. The aim of this review is to summarize the current knowledge on MSCs in treating thermal and radiation burns along with the specific scope of characterizing the biologic function of MSCs that help enhance wound healing in these chronic injuries.
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      PubDate: 2017-10-18T00:26:56Z
      DOI: 10.1016/j.addr.2017.10.003
       
  • Engineering nanomaterials to overcome the mucosal barrier by modulating
           surface properties
    • Authors: Lei Wu; Wei Shan; Zhirong Zhang; Yuan Huang
      Abstract: Publication date: Available online 5 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Lei Wu, Wei Shan, Zhirong Zhang, Yuan Huang
      Although nanotechnology has been investigated during recent years to increase the bioavailability and therapeutic effects of mucosal administrated drugs, numerous barriers (e.g., pH environment, enzymes and mucus) still limit the delivery efficiency. And the epithelium would also affect the systemic mucosal drug delivery. Amongst all the barriers, the protective mucus has drawn more and more attention, which strongly hinders the accessibility of nanovehicles to epithelium. Therefore, trials to conquer the mucus barrier have been designed using two controversial strategies: mucoadhesion and mucus-penetration. This review summarizes the influence of mucus layer on nanomaterials and introduces the modification strategies by modulating surface properties (i.e., hydrophilicity/hydrophobicity and surface charge) to overcome mucus barriers. Furthermore, it also reviews advanced modification methods to meet the different surface requirements of nanovehicles to overcome mucus and epithelium barriers in systemic mucosal delivery.
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      PubDate: 2017-10-18T00:26:56Z
      DOI: 10.1016/j.addr.2017.10.001
       
  • PDGF receptors in tumor stroma: Biological effects and associations with
           prognosis and response to treatment
    • Authors: Arne
      Abstract: Publication date: Available online 29 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Arne Östman
      Platelet-derived growth factor (PDGF) ligands and their receptors (PDGFRα and PDGFRβ) regulate mesenchymal cells, such as fibroblasts and pericytes. These cells are important constituents of tumor stroma where they impact on tumor growth, metastasis and drug response. Studies in model systems have demonstrated ability of the PDGF system to regulate the tumor-stimulatory effects of fibroblasts, as well as their ability to promote cancer cell migration and invasion. Animal studies imply PDGFR-signaling as a regulator of tumor drug uptake. Emerging correlative analyses of different tumor collections are identifying clinically relevant variations in stromal PDGFR status, and associations between PDGFR status in tumor stroma and survival. These associations could either relate to effects of stromal PDGFR signaling on the natural course of the disease or response to treatment. The availability of clinically approved PDGFR-inhibitory drugs suggest interesting possibilities for novel clinical studies, performed on selected patient sub-groups, which further exploits tumor stroma-derived PDGFR signaling.
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      PubDate: 2017-10-05T01:44:45Z
       
  • Clinical translation of stem cell based interventions for spinal cord
           injury- Are we there yet'
    • Authors: Harvinder S. Chhabra; Kanchan Sarda
      Abstract: Publication date: Available online 28 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Harvinder S. Chhabra, Kanchan Sarda
      Recent advances in basic science in research related to spinal cord injury (SCI) and regeneration have led to a variety of novel experimental therapeutics designed to promote functionally effective axonal regrowth and sprouting. Stem cell and other cellular interventions have gained lot of attention due to their immense potential of regeneration. These interventions have been tested for their efficacy in case of SCI both at the pre-clinical and clinical level. In this review we critically discuss the published literature on the cellular interventions for SCI and their clinical applications with respect to the strength of evidence established by these studies. The need to curb unethical practice of offering unproven stem cell “therapies” for SCI at a global level is also discussed.
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      PubDate: 2017-10-05T01:44:45Z
      DOI: 10.1016/j.addr.2017.09.021
       
  • Genome stability of programmed stem cell products
    • Authors: Ulrich Martin
      Abstract: Publication date: Available online 13 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Ulrich Martin
      Inherited and acquired genomic abnormalities are known to cause genetic diseases and contribute to cancer formation. Recent studies demonstrated a substantial mutational load in mouse and human embryonic and induced pluripotent stem cells (ESCs and iPSCs). Single nucleotide variants, copy number variations, and larger chromosomal abnormalities may influence the differentiation capacity of pluripotent stem cells and the functionality of their derivatives in disease modelling and drug screening, and are considered a serious risk for cellular therapies based on ESC or iPSC derivatives. This review discusses the types and origins of different genetic abnormalities in pluripotent stem cells, methods for their detection, and the mechanisms of development and enrichment during reprogramming and culture expansion.
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      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.004
       
  • (Re-)programming of subtype specific cardiomyocytes
    • Authors: Frauke Hausburg; Julia Jeannine Jung; Matti Hoch; Markus Wolfien; Arash Yavari; Christian Rimmbach; Robert David
      Abstract: Publication date: Available online 12 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Frauke Hausburg, Julia Jeannine Jung, Matti Hoch, Markus Wolfien, Arash Yavari, Christian Rimmbach, Robert David
      Adult cardiomyocytes (CMs) possess a highly restricted intrinsic regenerative potential — a major barrier to the effective treatment of a range of chronic degenerative cardiac disorders characterized by cellular loss and/or irreversible dysfunction and which underlies the majority of deaths in developed countries. Both stem cell programming and direct cell reprogramming hold promise as novel, potentially curative approaches to address this therapeutic challenge. The advent of induced pluripotent stem cells (iPSCs) has introduced a second pluripotent stem cell source besides embryonic stem cells (ESCs), enabling even autologous cardiomyocyte production. In addition, the recent achievement of directly reprogramming somatic cells into cardiomyocytes is likely to become of great importance. In either case, different clinical scenarios will require the generation of highly pure, specific cardiac cellular-subtypes. In this review, we discuss these themes as related to the cardiovascular stem cell and programming field, including a focus on the emergent topic of pacemaker cell generation for the development of biological pacemakers and in vitro drug testing.
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      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.005
       
  • Stem cell-based peripheral vascular regeneration
    • Authors: Yasuyuki Fujita; Atsuhiko Kawamoto
      Abstract: Publication date: Available online 11 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Yasuyuki Fujita, Atsuhiko Kawamoto
      Chronic critical limb ischemia (CLI) represents an end-stage manifestation of peripheral arterial disease (PAD). CLI patients are at very high risk of amputation and cardiovascular complications, leading to severe morbidity and mortality. Because many patients with CLI are ineligible for conventional revascularization procedures, it is urgently needed to explore alternative strategies to improve blood supply in the ischemic tissue. Although researchers initially focused on gene/protein therapy using proangiogenic growth factors/cytokines, recent discovery of somatic stem/progenitor cells including bone marrow (BM)-derived endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) has drastically developed the field of therapeutic angiogenesis for CLI. Overall, early phase clinical trials demonstrated that stem/progenitor cell therapies may be safe, feasible and potentially effective. However, only few late-phase clinical trials have been conducted. This review provides an overview of the preclinical and clinical reports to demonstrate the usefulness and the current limitations of the cell-based therapies.
      Graphical abstract image

      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.001
       
 
 
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