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Advanced Drug Delivery Reviews
Journal Prestige (SJR): 4.09
Citation Impact (citeScore): 13
Number of Followers: 193  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0169-409X - ISSN (Online) 1872-8294
Published by Elsevier Homepage  [3206 journals]
  • Advances and controversies in studying sunscreen delivery and toxicity
    • Abstract: Publication date: Available online 19 February 2020Source: Advanced Drug Delivery ReviewsAuthor(s): Miko Yamada, Yousuf Mohammed, Tarl Prow This review critically evaluates the sunscreen delivery and toxicity field. We chose to focus on approved sunscreens in this review. Optimal sunscreen use prevents skin cancer and photoageing but there is an important knowledge gap in sunscreen/skin interactions. Sunscreen delivery is a key for efficacy, but studying sunscreen delivery is not straightforward. We review the strengths and weaknesses of in vitro, excised skin and clinical approaches. Understanding positive and negative sunscreen effects on skin homeostasis is also challenging. The results in this field, especially in vitro testing, are controversial and experimental design varies widely which further supports disparities between some findings. We hypothesize that bias towards showing sunscreen toxicity to increase impact could be problematic. We explore that perception through a detailed review of experimental design, especially in cell culture models. Our conclusion is that emerging, non- and minimally invasive technologies are enabling new approaches to volunteer studies that could significantly improve knowledge of sunscreen delivery and interactions.Graphical abstractUnlabelled Image
  • Conjugated polymer nano-systems for hyperthermia, imaging and drug
    • Abstract: Publication date: Available online 28 January 2020Source: Advanced Drug Delivery ReviewsAuthor(s): Santu Sarkar, Nicole Levi-Polyachenko Hyperthermia has shown tremendous therapeutic efficiency in the treatment of cancer due to its controllability, minimal invasiveness and limited side effects compared to the conventional treatment techniques like surgery, radiotherapy and chemotherapy. To improve the precision of hyperthermia specifically to a tumor location, near infra-red (NIR) light activatable inorganic metal nanoparticles have served as effective photothermal therapy materials, but toxicity and non-biodegradability have limited their clinical applications. Conjugated polymer nanoparticles have overcome these limitations and are emerging as superior photothermal materials owing to their excellent light harvesting nature, biocompatibility and tunable absorption properties. In this review we focus on the development of organic conjugated polymers (polyaniline, polypyrrole, polydopamine etc.) and their nanoparticles, which have broad NIR absorption. Such materials elicit photothermal effects upon NIR stimulation and may also serve as carriers for delivery of therapeutic and contrast agents for combined therapy. Subsequently, the emergence of donor-acceptor based semiconducting polymer nanoparticles with strong absorbance that is tunable across the NIR have been shown to eradicate tumors by either hyperthermia alone or combined with other therapies. The design of multifunctional polymer nanoparticles that absorb near- or mid- infrared light for heat generation, as well as their diagnostic abilities for precise biomedical applications are highlighted.
  • Fatty acid metabolism in the progression and resolution of CNS disorders
    • Abstract: Publication date: Available online 25 January 2020Source: Advanced Drug Delivery ReviewsAuthor(s): Jeroen F.J. Bogie, Mansour Haidar, Gijs Kooij, Jerome J.A. Hendriks Recent advances in lipidomics and metabolomics have unveiled the complexity of fatty acid metabolism and the fatty acid lipidome in health and disease. A growing body of evidence indicates that imbalances in the metabolism and level of fatty acids drive the initiation and progression of central nervous system (CNS) disorders such as multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease. Here, we provide an in-depth overview on the impact of the β-oxidation, synthesis, desaturation, elongation, and peroxidation of fatty acids on the pathophysiology of these and other neurological disorders. Furthermore, we discuss the impact of individual fatty acids species, acquired through the diet or endogenously synthesized in mammals, on neuroinflammation, neurodegeneration, and CNS repair. The findings discussed in this review highlight the therapeutic potential of modulators of fatty acid metabolism and the fatty acid lipidome in CNS disorders, and underscore the diagnostic value of lipidome signatures in these diseases.Graphical abstractUnlabelled Image
  • Molecular and biological rationale of hyperthermia as radio- and
    • Abstract: Publication date: Available online 23 January 2020Source: Advanced Drug Delivery ReviewsAuthor(s): A.L. Oei, H.P. Kok, S.B. Oei, M.R. Horsman, L.J.A. Stalpers, N.A.P. Franken, J. Crezee Mild hyperthermia, local heating of the tumour up to temperatures
  • Towards chamber specific heart-on-a-chip for drug testing applications
    • Abstract: Publication date: Available online 7 January 2020Source: Advanced Drug Delivery ReviewsAuthor(s): Yimu Zhao, Naimeh Rafatian, Erika Yan Wang, Qinghua Wu, Benjamin F.L. Lai, Rick Xingze Lu, Houman Savoji, Milica Radisic Modeling of human organs has long been a task for scientists in order to lower the costs of therapeutic development and understand the pathological onset of human disease. For decades, despite marked differences in genetics and etiology, animal models remained the norm for drug discovery and disease modeling. Innovative biofabrication techniques have facilitated the development of organ-on-a-chip technology that has great potential to complement conventional animal models. However, human organ as a whole, more specifically the human heart, is difficult to regenerate in vitro, in terms of its chamber specific orientation and its electrical functional complexity. Recent progress with the development of induced pluripotent stem cell differentiation protocols, made recapitulating the complexity of the human heart possible through the generation of cells representative of atrial & ventricular tissue, the sinoatrial node, atrioventricular node and Purkinje fibers. Current heart-on-a-chip approaches incorporate biological, electrical, mechanical, and topographical cues to facilitate tissue maturation, therefore improving the predictive power for the chamber-specific therapeutic effects targeting adult human. In this review, we will give a summary of current advances in heart-on-a-chip technology and provide a comprehensive outlook on the challenges involved in the development of human physiologically relevant heart-on-a-chip.Graphical abstractUnlabelled Image
  • Ablative fractional laser-assisted treatments for keratinocyte carcinomas
           and its precursors–Clinical review and future perspectives
    • Abstract: Publication date: Available online 7 January 2020Source: Advanced Drug Delivery ReviewsAuthor(s): Andrés M. Erlendsson, Uffe H. Olesen, Merete Haedersdal, Anthony M. Rossi Keratinocyte carcinomas (KC) are the most common malignant human neoplasms. Although surgery and destructive approaches are first-line treatments, topical therapies are commonly used. Due to limited uptake of topical agents across the skin barrier, clearance rates are often sub-optimal. In pre-clinical investigations, ablative fractional laser (AFL)-assisted drug delivery has demonstrated improved uptake of topical drugs commonly used to treat KC. In 22 clinical trials, the effect of AFL-assisted treatments has been investigated for actinic keratosis (AK; n = 14), Bowen's disease (BD; n = 5), squamous cell carcinoma (n = 1), and basal cell carcinoma (n = 7). The most substantial evidence currently exists for AFL-assisted photodynamic therapy for the treatment of AK and BD. AFL improved 12-months follow-up clearance rates of photodynamic therapy from 45.0–51.0% to 78.5–84.8% for AK and from 50.0–55.3% to 87.0–87.5% for BD. AFL-assisted pharmacological therapy is a promising tool for optimizing topical treatments of KC and its precursor lesions. Future developments include AFL-assisted immune activation, changing drug administration route of systemic therapies, and utilizing drug chemo-combinations.
  • Sphingolipids in Alzheimer's disease, how can we target them'
    • Abstract: Publication date: Available online 3 January 2020Source: Advanced Drug Delivery ReviewsAuthor(s): Simone M. Crivelli, Caterina Giovagnoni, Lars Visseren, Anna-Lena Scheithauer, Nienke de Wit, Sandra den Hoedt, Mario Losen, Monique T. Mulder, Jochen Walter, Helga E. de Vries, Erhard Bieberich, Pilar Martinez-Martinez Altered levels of sphingolipids and their metabolites in the brain, and the related downstream effects on the neuronal homeostasis and immune system, provide a framework for understanding mechanisms in neurodegenerative disorders and for developing new intervention strategies. In this review we will discuss: the metabolites of sphingolipids that function as second messengers; and functional aberrations of the pathway resulting in Alzheimer's disease (AD) pathophysiology. Focusing on the central product of the sphingolipid pathway ceramide, we described approaches to pharmacologically decrease ceramide levels in the brain and we argue on how the sphingolipid pathway may represent a new framework for developing novel intervention strategies in AD. We will also highlight the possible use of clinical and non-clinical drugs to modulate sphingolipid pathways and sphingolipid-related biological cascades.Graphical abstractUnlabelled Image
  • Non-transdermal microneedles for advanced drug delivery
    • Abstract: Publication date: Available online 16 December 2019Source: Advanced Drug Delivery ReviewsAuthor(s): KangJu Lee, Marcus J. Goudie, Peyton Tebon, Wujin Sun, Zhimin Luo, Junmin Lee, Shiming Zhang, Kirsten Fetah, Han-Jun Kim, Yumeng Xue, Mohammad Ali Darabi, Samad Ahadian, Einollah Sarikhani, WonHyoung Ryu, Zhen Gu, Paul S. Weiss, Mehmet R. Dokmeci, Nureddin Ashammakhi, Ali Khademhosseini Microneedles (MNs) have been used to deliver drugs for over two decades. These platforms have been proven to increase transdermal drug delivery efficiency dramatically by penetrating restrictive tissue barriers in a minimally invasive manner. While much of the early development of MNs focused on transdermal drug delivery, this technology can be applied to a variety of other non-transdermal biomedical applications. Several variations, such as multi-layer or hollow MNs, have been developed to cater to the needs of specific applications. The heterogeneity in the design of MNs has demanded similar variety in their fabrication methods; the most common methods include micromolding and drawing lithography. Numerous materials have been explored for MN fabrication which range from biocompatible ceramics and metals to natural and synthetic biodegradable polymers. Recent advances in MN engineering have diversified MNs to include unique shapes, materials, and mechanical properties that can be tailored for organ-specific applications. In this review, we discuss the design and creation of modern MNs that aim to surpass the biological barriers of non-transdermal drug delivery in ocular, vascular, oral, and mucosal tissue.Graphical abstractUnlabelled Image
  • Drug delivery to macrophages: A review of targeting drugs and drug
           carriers to macrophages for inflammatory diseases
    • Abstract: Publication date: Available online 6 December 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Wei He, Neha Kapate, C. Wyatt Shields, Samir Mitragotri Macrophages play a key role in defending against foreign pathogens, healing wounds, and regulating tissue homeostasis. Driving this versatility is their phenotypic plasticity, which enables macrophages to respond to subtle cues in tightly coordinated ways. However, when this coordination is disrupted, macrophages can aid the progression of numerous diseases, including cancer, cardiovascular disease, and autoimmune disease. The central link between these disorders is aberrant macrophage polarization, which misguides their functional programs, secretory products, and regulation of the surrounding tissue microenvironment. As a result of their important and deterministic roles in both health and disease, macrophages have gained considerable attention as targets for drug delivery. Here, we discuss the role of macrophages in the initiation and progression of various inflammatory diseases, summarize the leading drugs used to regulate macrophages, and review drug delivery systems designed to target macrophages. We emphasize strategies that are approved for clinical use or are poised for clinical investigation. Finally, we provide a prospectus of the future of macrophage-targeted drug delivery systems.Graphical abstractUnlabelled Image
  • The blood-brain barrier: Physiology and strategies for drug delivery
    • Abstract: Publication date: Available online 29 November 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Rucha Pandit, Liyu Chen, Jürgen Götz The blood-brain barrier (BBB) is a dynamic structure that functions as a gatekeeper, reflecting the unique requirements of the brain. In this review, following a brief historical overview of how the concepts of the BBB and the neurovascular unit (NVU) developed, we describe its physiology and architecture, which pose a particular challenge to therapeutic intervention. We then discuss how the restrictive nature of this barrier can be overcome for the delivery of therapeutic agents. Alterations to drug formulation offer one option, in part by utilizing distinct transport modes; another is invasive or non-invasive strategies to bypass the BBB. An emerging non-invasive technology for targeted drug delivery is focused ultrasound that allows for the safe and reversible disruption of the BBB. We discuss the underlying mechanisms and provide an outlook, emphasizing the need for more research into the NVU and investment in innovative technologies to overcome the BBB for drug delivery.Graphical abstractUnlabelled Image
  • ADDR Editor's Collection 2019
    • Abstract: Publication date: November–December 2019Source: Advanced Drug Delivery Reviews, Volumes 151–152Author(s): Hamidreza Ghandehari
  • Fluorescence anisotropy imaging in drug discovery
    • Abstract: Publication date: November–December 2019Source: Advanced Drug Delivery Reviews, Volumes 151–152Author(s): Claudio Vinegoni, Paolo Fumene Feruglio, Ignacy Gryczynski, Ralph Mazitschek, Ralph Weissleder Non-invasive measurement of drug-target engagement can provide critical insights in the molecular pharmacology of small molecule drugs. Fluorescence polarization/fluorescence anisotropy measurements are commonly employed in protein/cell screening assays. However, the expansion of such measurements to the in vivo setting has proven difficult until recently. With the advent of high-resolution fluorescence anisotropy microscopy it is now possible to perform kinetic measurements of intracellular drug distribution and target engagement in commonly used mouse models. In this review we discuss the background, current advances and future perspectives in intravital fluorescence anisotropy measurements to derive pharmacokinetic and pharmacodynamic measurements in single cells and whole organs.Graphical abstractUnlabelled Image
  • Sequential drug/gene delivery in tissue engineering & regenerative
    • Abstract: Publication date: September–October 2019Source: Advanced Drug Delivery Reviews, Volumes 149–150Author(s): Sing Yian Chew
  • Adenosine and lipids: A forced marriage or a love match'
    • Abstract: Publication date: Available online 21 February 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Marie Rouquette, Sinda Lepetre-Mouelhi, Patrick Couvreur Adenosine is a fascinating compound, crucial in many biochemical processes: this ubiquitous nucleoside serves as an essential building block of RNA, is also a component of ATP and regulates numerous pathophysiological mechanisms via binding to four extracellular receptors. Due to its hydrophilic nature, it belongs to a different world than lipids, and has no affinity for them. Since the 1970's, however, new discoveries have emerged and prompted the scientific community to associate adenosine with the lipid family, especially via liposomal preparations and bioconjugation. This seems to be an arranged marriage, but could it turn into a true love match? This review considered all types of unions established between adenosine and lipids. Even though exciting supramolecular structures were observed with adenosine-lipid conjugates, as well as with liposomal preparations which resulted in promising pre-clinical results, the translation of these technologies to the clinic is still limited.Graphical abstractUnlabelled Image
  • Chronopharmacology of glucocorticoids
    • Abstract: Publication date: Available online 21 February 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Megerle L. Scherholz, Naomi Schlesinger, Ioannis P. Androulakis Glucocorticoids influence a wide array of metabolic, anti-inflammatory, immunosuppressive, and cognitive signaling processes, playing an important role in homeostasis and preservation of normal organ function. Synthesis is regulated by the hypothalamic-pituitary-adrenal (HPA) axis of which cortisol is the primary glucocorticoid in humans. Synthetic glucocorticoids are important pharmacological agents that augment the anti-inflammatory and immunosuppressive properties of endogenous cortisol and are widely used for the treatment of asthma, Crohn's disease, and rheumatoid arthritis, amongst other chronic conditions. The homeostatic activity of cortisol is disrupted by the administration of synthetic glucocorticoids and so there is interest in developing treatment options that minimize HPA axis disturbance while maintaining the pharmacological effects. Studies suggest that optimizing drug administration time can achieve this goal. The present review provides an overview of endogenous glucocorticoid activity and recent advances in treatment options that have further improved patient safety and efficacy with an emphasis on chronopharmacology.Graphical abstractUnlabelled Image
  • Technologies for intrapericardial delivery of therapeutics and cells
    • Abstract: Publication date: Available online 21 February 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Carly S. Filgueira, Stephen R. Igo, Dennis K. Wang, Matteo Hirsch, Daryl G. Schulz, Brian A. Bruckner, Alessandro Grattoni The pericardium, which surrounds the heart, provides a unique enclosed volume and a site for the delivery of agents to the heart and coronary arteries. While strategies for targeting the delivery of therapeutics to the heart are lacking, various technologies and nanodelivery approaches are emerging as promising methods for site specific delivery to increase therapeutic myocardial retention, efficacy, and bioactivity, while decreasing undesired systemic effects. Here, we provide a literature review of various approaches for intrapericardial delivery of agents. Emphasis is given to sustained delivery approaches (pumps and catheters) and localized release (patches, drug eluting stents, and support devices and meshes). Further, minimally invasive access techniques, pericardial access devices, pericardial washout and fluid analysis, as well as therapeutic and cell delivery vehicles are presented. Finally, several promising new therapeutic targets to treat heart diseases are highlighted.Graphical abstractUnlabelled Image
  • Cathepsin-sensitive nanoscale drug delivery systems for cancer therapy and
           other diseases
    • Abstract: Publication date: Available online 26 January 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Divya Dheer, Julien Nicolas, Ravi Shankar Cathepsins are an important category of enzymes that have attracted great attention for the delivery of drugs to improve the therapeutic outcome of a broad range of nanoscale drug delivery systems. These proteases can be utilized for instance through actuation of polymer-drug conjugates (e.g., triggering the drug release) to bypass limitations of many drug candidates. A substantial amount of work has been witnessed in the design and the evaluation of Cathepsin-sensitive drug delivery systems, especially based on the tetra-peptide sequence (Gly-Phe-Leu-Gly, GFLG) which has been extensively used as a spacer that can be cleaved in the presence of Cathepsin B. This Review Article will give an in-depth overview of the design and the biological evaluation of Cathepsin-sensitive drug delivery systems and their application in different pathologies including cancer before discussing Cathepsin B-cleavable prodrugs under clinical trials.Graphical abstractUnlabelled Image
  • Zebrafish as a preclinical in vivo screening model for
    • Abstract: Publication date: Available online 4 January 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Sandro Sieber, Philip Grossen, Jeroen Bussmann, Frederick Campbell, Alexander Kros, Dominik Witzigmann, Jörg Huwyler The interactions of nanomedicines with biological environments is heavily influenced by their physicochemical properties. Formulation design and optimization are therefore key steps towards successful nanomedicine development. Unfortunately, detailed assessment of nanomedicine formulations, at a macromolecular level, in rodents is severely limited by the restricted imaging possibilities within these animals. Moreover, rodent in vivo studies are time consuming and expensive, limiting the number of formulations that can be practically assessed in any one study. Consequently, screening and optimisation of nanomedicine formulations is most commonly performed in surrogate biological model systems, such as human-derived cell cultures. However, despite the time and cost advantages of classical in vitro models, these artificial systems fail to reflect and mimic the complex biological situation a nanomedicine will encounter in vivo. This has acutely hampered the selection of potentially successful nanomedicines for subsequent rodent in vivo studies. Recently, zebrafish have emerged as a promising in vivo model, within nanomedicine development pipelines, by offering opportunities to quickly screen nanomedicines under in vivo conditions and in a cost-effective manner so as to bridge the current gap between in vitro and rodent studies. In this review, we outline several advantageous features of the zebrafish model, such as biological conservation, imaging modalities, availability of genetic tools and disease models, as well as their various applications in nanomedicine development. Critical experimental parameters are discussed and the most beneficial applications of the zebrafish model, in the context of nanomedicine development, are highlighted.Graphical abstractUnlabelled Image
  • Editorial
    • Abstract: Publication date: Available online 21 January 2012Source: Advanced Drug Delivery ReviewsAuthor(s): Raphaël Lévy, Mathias Brust
  • Imaging and quantifying drug delivery in skin – Part 1: Autoradiography
           and mass spectrometry imaging
    • Abstract: Publication date: Available online 26 November 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Sébastien Grégoire, Gustavo S. Luengo, Philippe Hallegot, Ana-Maria Pena, Xueqin Chen, Thomas Bornschlögl, Kin F. Chan, Isaac Pence, Peyman Obeidy, Amin Feizpour, Sinyoung Jeong, Conor L. Evans In this two parts review we present an up-do-date description of different imaging methods available to map the localization of drugs on skin as a complement of established ex-vivo absorption studies. This first part deals with invasive methods and are grouped in two classes according to their underlying principles: i) methods using radioactivity such as autoradiography and ii) mass spectrometry methods such as MALDI and SIMS. For each method, a description of the principle is given along with example applications of imaging and quantifying drug delivery in human skin. Thanks to these techniques a better assessment of the fate of drugs is obtained, its localization on a particular skin structure, its potential accumulation, etc. A critical comparison in terms of capabilities, sensibility and practical applicability is included that will help the reader to select the most appropriate technique depending on the particular problem to be solved.Graphical abstractUnlabelled Image
  • Rational designs of in vivo CRISPR-Cas delivery systems
    • Abstract: Publication date: Available online 21 November 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Cong-Fei Xu, Guo-Jun Chen, Ying-Li Luo, Yue Zhang, Gui Zhao, Zi-Dong Lu, Anna Czarna, Zhen Gu, Jun Wang The CRISPR-Cas system initiated a revolution in genome editing when it was, for the first time, demonstrated success in the mammalian cells. Today, scientists are able to readily edit the genome, regulate gene transcription, engineer posttranscriptional events, and image nucleic acids using CRISPR-Cas-based tools. However, to efficiently transport CRISPR-Cas into target tissues/cells remains challenging due to many extra- and intra-cellular barriers, therefore largely limiting the applications of CRISPR-based therapeutics in vivo. In this review, we summarize the features of plasmid-, RNA- and ribonucleoprotein (RNP)-based CRISPR-Cas therapeutics. Then, we survey the current in vivo delivery systems. Finally, we specify the requirements for efficient in vivo delivery in clinical settings, and highlight both efficiency and safety for different CRISPR-Cas tools.Graphical abstractUnlabelled Image
  • Sequential drug delivery for liver diseases
    • Abstract: Publication date: Available online 15 November 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Xiaozhong Huang, Fan Lee, Yao Teng, Corey Bryen Lingam, Zijian Chen, Min Sun, Ziwei Song, Gowri M. Balachander, Hwa Liang Leo, Qiongyu Guo, Imran Shah, Hanry Yu The liver performs critical physiological functions such as metabolism/detoxification and blood homeostasis/biliary excretion. A high degree of blood access means that a drug’s resident time in any cell is relatively short. This short drug exposure to cells requires local sequential delivery of multiple drugs for optimal efficacy, potency, and safety. The high metabolism and excretion of drugs also impose both technical challenges and opportunities to sequential drug delivery. This review provides an overview of the sequential events in liver regeneration and the related liver diseases. Using selected examples of liver cancer, hepatitis B viral infection, fatty liver diseases, and drug-induced liver injury, we highlight efforts made for the sequential delivery of small and macromolecular drugs through different biomaterials, cells, and microdevice-based delivery platforms that allow fast delivery kinetics and rapid drug switching. As this is a nascent area of development, we extrapolate and compare the results with other sequential drug delivery studies to suggest possible application in liver diseases, wherever appropriate.Graphical abstractUnlabelled Image
  • Topical treatments for skin cancer
    • Abstract: Publication date: Available online 6 November 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Jason K. Cullen, Jacinta L. Simmons, Peter G. Parsons, Glen M. Boyle Skin cancer is a broad term used to describe a number of different malignant indications of the skin. Skin cancers mostly comprise of the keratinocyte cancers [Basal Cell Carcinoma (BCC) and cutaneous Squamous Cell Carcinoma (SCC)], and melanoma. Surgical excision of these malignancies has been the preferred treatment of patients for decades. However, the decision to perform surgery can be affected by various considerations, including co-morbidities of the patient, the anatomical site of the lesion and potential intolerance for repeated excisions. Topical treatment of skin cancer may therefore be more appropriate in certain instances. Topical treatment potentially allows for higher drug levels at the tumor site, and may result in less overall toxicity than systemic agents. This review will specifically address the current agents used in topical treatment of skin cancers, and introduce emerging treatments from the natural product field that may also find utility in these indications.Graphical abstractUnlabelled Image
  • Silk fibroin for skin injury repair: Where do things stand'
    • Abstract: Publication date: Available online 31 October 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Mazaher Gholipourmalekabadi, Sunaina Sapru, Ali Samadikuchaksaraei, Rui L. Reis, David L. Kaplan, Subhas C. Kundu Several synthetic and natural materials are used in soft tissue engineering and regenerative medicine with varying degrees of success. Among them, silkworm silk protein fibroin, a naturally occurring protein-based biomaterial, exhibits many promising characteristics such as biocompatibility, controllable biodegradability, tunable mechanical properties, aqueous preparation, minimal inflammation in host tissue, low cost and ease of use. Silk fibroin is often used alone or in combination with other materials in various formats and is also a promising delivery system for bioactive compounds as part of such repair scenarios. These properties make silk fibroin an excellent biomaterial for skin tissue engineering and repair applications. This review focuses on the promising characteristics and recent advances in the use of silk fibroin for skin wound healing and/or soft-tissue repair applications. The benefits and limitations of silk fibroin as a scaffolding biomaterial in this context are also discussed.Statement of significanceSilk protein fibroin is a natural biomaterial with important biological and mechanical properties for soft tissue engineering applications. Silk fibroin is obtained from silkworms and can be purified using alkali or enzyme based degumming (removal of glue protein sericin) procedures. Fibroin is used alone or in combination with other materials in different scaffold forms, such as nanofibrous mats, hydrogels, sponges or films tailored for specific applications. The investigations carried out using silk fibroin or its blends in skin tissue engineering have increased dramatically in recent years due to the advantages of this unique biomaterial. This review focuses on the promising characteristics of silk fibroin for skin wound healing and/or soft-tissue repair applications.Graphical abstractSilkworm silk fibroin is a well-established natural protein in the realm of biomaterials with an array of matrices in its repository. These range from primary bio coating to state of the art, bioprinting en route for creating an advanced graft for diversified biomedical applications. Augmenting these matrices by incorporating functional traits like delivery of bioactive molecules/compounds (growth factor, drug, antibiotic, gene or cell) or conductivity make them smart matrices for skin tissue regeneration and skin repair.Unlabelled Image
  • Intradermal and transdermal drug delivery using microneedles –
    • Abstract: Publication date: Available online 18 October 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Akmal H. Sabri, Yujin Kim, Maria Marlow, David J. Scurr, Joel Segal, Ajay K. Banga, Leonid Kagan, Jong Bong Lee The progress in microneedle research is evidenced by the transition from simple ‘poke and patch’ solid microneedles fabricated from silicon and stainless steel to the development of bioresponsive systems such as hydrogel-forming and dissolving microneedles. In this review, we provide an outline on various microneedle fabrication techniques which are currently employed. As a range of factors, including materials, geometry and design of the microneedles, affect the performance, it is important to understand the relationships between them and the resulting delivery of therapeutics. Accordingly, there is a need for appropriate methodologies and techniques for characterization and evaluation of microneedle performance, which will also be discussed. As the research expands, it has been observed that therapeutics delivered via microneedles has gained expedited access to the lymphatics, which makes them a favorable delivery method for targeting the lymphatic system. Such opportunity is valuable in the area of vaccination and treatment of lymphatic disorders, which is the final focus of the review.Graphical abstractUnlabelled Image
  • Fundamentals of fractional laser-assisted drug delivery: An in-depth guide
           to experimental methodology and data interpretation
    • Abstract: Publication date: Available online 16 October 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Emily Wenande, R. Rox Anderson, Merete Haedersdal In the decade since their advent, ablative fractional lasers have emerged as powerful tools to enhance drug delivery to and through the skin. Effective and highly customizable, laser-assisted drug delivery (LADD) has led to improved therapeutic outcomes for several medical indications. However, for LADD to reach maturity as a standard treatment technique, a greater appreciation of its underlying science is needed. This work aims to provide an in-depth guide to the technology's fundamental principles, experimental methodology and unique aspects of LADD data interpretation. We show that drug's physicochemical properties including solubility, molecular weight and tissue binding behavior, are crucial determinants of how laser channel morphology influences topical delivery. Furthermore, we identify strengths and limitations of experimental models and drug detection techniques, interrogating the usefulness of in vitro data in predicting LADD in vivo. By compiling insights from over 75 studies, we ultimately devise an approach for intelligent application of LADD, supporting its implementation in the clinical setting.Graphical abstractUnlabelled Image
  • Physical and chemical profiles of nanoparticles for lymphatic targeting
    • Abstract: Publication date: Available online 15 October 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Xiyu Ke, Gregory P. Howard, Haoyu Tang, Bei Cheng, May Tun Saung, José L. Santos, Hai-Quan Mao Nanoparticles (NPs) have been gaining prominence as delivery vehicles for modulating immune responses to improve treatments against cancer and autoimmune diseases, enhancing tissue regeneration capacity, and potentiating vaccination efficacy. Various engineering approaches have been extensively explored to control the NP physical and chemical properties including particle size, shape, surface charge, hydrophobicity, rigidity and surface targeting ligands to modulate immune responses. This review examines a specific set of physical and chemical characteristics of NPs that enable efficient delivery targeted to secondary lymphoid tissues, specifically the lymph nodes and immune cells. A critical analysis of the structure-property-function relationship will facilitate further efforts to engineer new NPs with unique functionalities, identify novel utilities, and improve the clinical translation of NP formulations for immunotherapy.Graphical abstractUnlabelled Image
  • Carbohydrate-based nanocarriers and their application to target
           macrophages and deliver antimicrobial agents
    • Abstract: Publication date: Available online 10 September 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Tamim Mosaiab, Dylan Farr, Milton J. Kiefel, Todd A. Houston Many deadly infections are produced by microorganisms capable of sustained survival in macrophages. This reduces exposure to chemotherapy, prevents immune detection, and is akin to criminals hiding in police stations. Therefore, the use of glyco-nanoparticles (GNPs) as carriers of therapeutic agents is a burgeoning field. Such an approach can enhance the penetration of drugs into macrophages with specific carbohydrate targeting molecules on the nanocarrier to interact with macrophage lectins. Carbohydrates are natural biological molecules and the key constituents in a large variety of biological events such as cellular communication, infection, inflammation, enzyme trafficking, cellular migration, cancer metastasis and immune functions. The prominent characteristics of carbohydrates including biodegradability, biocompatibility, hydrophilicity and the highly specific interaction of targeting cell-surface receptors support their potential application to drug delivery system (DDS). This review presents the 21st century development of carbohydrate-based nanocarriers for drug targeting of therapeutic agents for diseases localized in macrophages. The significance of natural carbohydrate derived nanoparticles (GNPs) as anti-microbial drug carriers is highlighted in several areas of treatment including tuberculosis, salmonellosis, leishmaniasis, candidiasis, and HIV/AIDS.Graphical abstractUnlabelled Image
  • Pharmacokinetics of nanotechnology-based formulations in pediatric
    • Abstract: Publication date: Available online 5 September 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Venkata Yellepeddi, Andrea Joseph, Elizabeth Nance The development of therapeutics for pediatric use has advanced in the last few decades. However, off-label use of adult medications in pediatrics remains a significant clinical problem. Furthermore, the development of therapeutics for pediatrics is challenged by the lack of pharmacokinetic (PK) data in the pediatric population. To promote the development of therapeutics for pediatrics, the United States Pediatric Formulation Initiative recommended the investigation of nanotechnology-based delivery systems. Therefore, in this review, we provided comprehensive information on the PK of nanotechnology-based formulations from preclinical and clinical studies in pediatrics. Specifically, we discuss the relationship between formulation parameters of nanoformulations and PK of the encapsulated drug in the context of pediatrics. We review nanoformulations that include dendrimers, liposomes, polymeric long-acting injectables (LAIs), nanocrystals, inorganic nanoparticles, polymeric micelles, and protein nanoparticles. In addition, we describe the importance and need of PK modeling and simulation approaches used in predicting PK of nanoformulations for pediatric applications.Graphical abstractUnlabelled Image
  • Lessons learned from intervertebral disc pathophysiology to guide rational
           design of sequential delivery systems for therapeutic biological factors
    • Abstract: Publication date: Available online 21 August 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Leslie Frapin, Johann Clouet, Vianney Delplace, Marion Fusellier, Jérôme Guicheux, Catherine Le Visage Intervertebral disc (IVD) degeneration has been associated with low back pain, which is a major musculoskeletal disorder and socio-economic problem that affects as many as 600 million patients worldwide. Here, we first review the current knowledge of IVD physiology and physiopathological processes in terms of homeostasis regulation and consecutive events that lead to tissue degeneration. Recent progress with IVD restoration by anti-catabolic or pro-anabolic approaches are then analyzed, as are the design of macro-, micro-, and nano-platforms to control the delivery of such therapeutic agents. Finally, we hypothesize that a sequential delivery strategy that i) firstly targets the inflammatory, pro-catabolic microenvironment with release of anti-inflammatory or anti-catabolic cytokines; ii) secondly increases cell density in the less hostile microenvironment by endogenous cell recruitment or exogenous cell injection, and finally iii) enhances cellular synthesis of extracellular matrix with release of pro-anabolic factors, would constitute an innovative yet challenging approach to IVD regeneration.Graphical abstractUnlabelled Image
  • Hydrogel vehicles for sequential delivery of protein drugs to promote
           vascular regeneration
    • Abstract: Publication date: Available online 14 August 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Zhao Wei, Eugenia Volkova, Michael R. Blatchley, Sharon Gerecht In recent years, as the mechanisms of vasculogenesis and angiogenesis have been uncovered, the functions of various pro-angiogenic growth factors (GFs) and cytokines have been identified. Therefore, therapeutic angiogenesis, by delivery of GFs, has been sought as a treatment for many vascular diseases. However, direct injection of these protein drugs has proven to have limited clinical success due to their short half-lives and systemic off-target effects. To overcome this, hydrogel carriers have been developed to conjugate single or multiple GFs with controllable, sustained, and localized delivery. However, these attempts have failed to account for the temporal complexity of natural angiogenic pathways, resulting in limited therapeutic effects. Recently, the emerging ideas of optimal sequential delivery of multiple GFs have been suggested to better mimic the biological processes and to enhance therapeutic angiogenesis. Incorporating sequential release into drug delivery platforms will likely promote the formation of neovasculature and generate vast therapeutic potential.Graphical abstractUnlabelled Image
  • Nanomedicines - Tiny particles and big challenges
    • Abstract: Publication date: Available online 19 June 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Margareth R.C. Marques, Qiuyi Choo, Mukul Ashtikar, Thais Correa Rocha, Susanne Bremer-Hoffmann, Matthias G. Wacker After decades of research, nanotechnology has been used in a broad array of biomedical products including medical devices, drug products, drug substances, and pharmaceutical-grade excipients. But like many great achievements in science, there is a fine balance between the risks and opportunities of this new technology. Some materials and surface structures in the nanosize range can exert unexpected toxicities and merit a more detailed safety assessment. Regulatory agencies such as the United States Food and Drug Administration or the European Medicines Agency have started dealing with the potential risks posed by nanomaterials. Considering that a thorough characterization is one of the key aspects of controlling such risks this review presents the regulatory background of nanosafety assessment and provides some practical advice on how to characterize nanomaterials and drug formulations. Further, the challenges of how to maintain and monitor pharmaceutical quality through a highly complex production processes will be discussed.Graphical abstractUnlabelled Image
  • Intrinsic cancer vaccination
    • Abstract: Publication date: Available online 24 May 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Yoosoo Yang, Gi-Hoon Nam, Gi Beom Kim, Yoon Kyoung Kim, In-San Kim Immunotherapy is revolutionizing the treatment of cancer, and the current immunotherapeutics have remarkably improved the outcomes for some cancer patients. However, we still need answers for patients with immunologically cold tumors that do not benefit from the current immunotherapy treatments. Here, we suggest a novel strategy that is based on using a very old and sophisticated system for cancer immunotherapy, namely “intrinsic cancer vaccination”, which seeks to awaken our own immune system to activate tumor-specific T cells. To do this, we must take advantage of the genetic instability of cancer cells and the expression of cancer cell neoantigens to trigger immunity against cancer cells. It will be necessary to not only enhance the phagocytosis of cancer cells by antigen presenting cells but also induce immunogenic cancer cell death and the subsequent immunogenic clearance, cross-priming and generation of tumor-specific T cells. This strategy will allow us to avoid using known tumor-specific antigens, ex vivo manipulation or adoptive cell therapy; rather, we will efficiently present cancer cell neoantigens to our immune system and propagate the cancer-immunity cycle. This strategy simply follows the natural cycle of cancer-immunity from its very first step, and therefore could be combined with any other treatment modality to yield enhanced efficacy.Graphical abstractUnlabelled Image
  • Sequential drug delivery to modulate macrophage behavior and enhance
           implant integration
    • Abstract: Publication date: Available online 16 May 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Erin M. O'Brien, Gregory E. Risser, Kara L. Spiller Macrophages are major upstream regulators of the inflammatory response to implanted biomaterials. Sequential functions of distinct macrophage phenotypes are essential to the normal tissue repair process, which ideally results in vascularization and integration of implants. Improper timing of M1 or M2 macrophage activation results in dysfunctional healing in the form of chronic inflammation or fibrous encapsulation of the implant. Thus, biphasic drug delivery systems that modulate macrophage behavior are an appealing approach to promoting implant integration. In this review, we describe the timing and roles of macrophage phenotypes in healing, then highlight current drug delivery systems designed to sequentially modulate macrophage behavior.Graphical abstractUnlabelled Image
  • The significance of artificial intelligence in drug delivery system design
    • Abstract: Publication date: Available online 6 May 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Parichehr Hassanzadeh, Fatemeh Atyabi, Rassoul Dinarvand Over the last decade, increasing interest has been attracted towards the application of artificial intelligence (AI) technology for analyzing and interpreting the biological or genetic information, accelerated drug discovery, and identification of the selective small-molecule modulators or rare molecules and prediction of their behavior. Application of the automated workflows and databases for rapid analysis of the huge amounts of data and artificial neural networks (ANNs) for development of the novel hypotheses and treatment strategies, prediction of disease progression, and evaluation of the pharmacological profiles of drug candidates may significantly improve treatment outcomes. Target fishing (TF) by rapid prediction or identification of the biological targets might be of great help for linking targets to the novel compounds. AI and TF methods in association with human expertise may indeed revolutionize the current theranostic strategies, meanwhile, validation approaches are necessary to overcome the potential challenges and ensure higher accuracy. In this review, the significance of AI and TF in the development of drugs and delivery systems and the potential challenging issues have been highlighted.Graphical abstractUnlabelled Image
  • Thiolated polymers: Bioinspired polymers utilizing one of the most
           important bridging structures in nature
    • Abstract: Publication date: Available online 25 April 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Christina Leichner, Max Jelkmann, Andreas Bernkop-Schnürch Thiolated polymers designated “thiomers” are obtained by covalent attachment of thiol functionalities on the polymeric backbone of polymers. In 1998 these polymers were first described as mucoadhesive and in situ gelling compounds forming disulfide bonds with cysteine-rich substructures of mucus glycoproteins and crosslinking through inter- and intrachain disulfide bond formation. In the following, it was shown that thiomers are able to form disulfides with keratins and membrane-associated proteins exhibiting also cysteine-rich substructures. Furthermore, permeation enhancing, enzyme inhibiting and efflux pump inhibiting properties were demonstrated. Because of these capabilities thiomers are promising tools for drug delivery guaranteeing a strongly prolonged residence time as well as sustained release on mucosal membranes. Apart from that, thiomers are used as drugs per se. In particular, for treatment of dry eye syndrome various thiolated polymers are in development and a first product has already reached the market. Within this review an overview about the thiomer-technology and its potential for different applications is provided discussing especially the outcome of studies in non-rodent animal models and that of numerous clinical trials. Moreover, an overview on product developments is given.Graphical abstractThe great potential of thiolated polymers for life sciences might be described in the best way by the simple imagination of protein chemistry with and without cysteineUnlabelled Image
  • Drug therapies and delivery mechanisms to treat perturbed skin wound
    • Abstract: Publication date: Available online 6 April 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Jiah Shin Chin, Leigh Madden, Sing Yian Chew, David L. Becker Acute wound healing is an orderly process of four overlapping events: haemostasis, inflammation, proliferation and remodelling. A drug delivery system with a temporal control of release could promote each of these events sequentially. However, acute wound healing normally proceeds very well in healthy individuals and there is little need to promote it. In the elderly and diabetics however, healing is often slow and wounds can become chronic and we need to promote their healing. Targeting the events of acute wound healing would not be appropriate for a chronic wound, which have stalled in the proinflammatory phase. They also have many additional problems such as poor circulation, low oxygen, high levels of leukocytes, high reactive oxygen species, high levels of proteolytic enzymes, high levels of proinflammatory cytokines, bacterial infection and high pH. The future challenge will be to tackle each of these negative factors to create a wound environment conducive to healing.Graphical abstractUnlabelled Image
  • Scaffold-mediated sequential drug/gene delivery to promote nerve
           regeneration and remyelination following traumatic nerve injuries
    • Abstract: Publication date: Available online 22 March 2019Source: Advanced Drug Delivery ReviewsAuthor(s): William Ong, Coline Pinese, Sing Yian Chew Neural tissue regeneration following traumatic injuries is often subpar. As a result, the field of neural tissue engineering has evolved to find therapeutic interventions and has seen promising outcomes. However, robust nerve and myelin regeneration remain elusive. One possible reason may be the fact that tissue regeneration often follows a complex sequence of events in a temporally-controlled manner. Although several other fields of tissue engineering have begun to recognise the importance of delivering two or more biomolecules sequentially for more complete tissue regeneration, such serial delivery of biomolecules in neural tissue engineering remains limited. This review aims to highlight the need for sequential delivery to enhance nerve regeneration and remyelination after traumatic injuries in the central nervous system, using spinal cord injuries as an example. In addition, possible methods to attain temporally-controlled drug/gene delivery are also discussed for effective neural tissue regeneration.Graphical abstractUnlabelled Image
  • Lyophilized liposome-based parenteral drug development: Reviewing complex
           product design strategies and current regulatory environments
    • Abstract: Publication date: Available online 18 March 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Yuwei Wang, David W. Grainger Given the successful entry of several liposomal drug products into market, and some with decades of clinical efficacy, liposomal drug delivery systems have proven capabilities to overcome certain limitations of traditional drug delivery, especially for toxic and biologic drugs. This experience has helped promote new liposomal approaches to emerging drug classes and current therapeutic challenges. All approved liposomal dosage forms are parenteral formulations, a pathway demonstrating greatest safety and efficacy to date. Due to the intrinsic instability of aqueous liposomal dispersions, lyophilization is commonly applied as an important solution to improve liposomal drug stability, and facilitate transportation, storage and improve product shelf-life. While lyophilization is a mature pharmaceutical technology, liposome-specific lyophilization platforms must be developed using particular lyophilization experience and strategies. This review provides an overview of liposome formulation-specific lyophilization approaches for parenteral use, excipients used exclusively in liposomal parenteral products, lyophilized liposome formulation design and process development, long-term storage, and current regulatory guidance for liposome drug products. Readers should capture a comprehensive understanding of formulation and process variables and strategies for developing parenterally administered liposomal drugs.Graphical abstractUnlabelled Image
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