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Adv Drug Deliv Rev 2021 Jun 21:113845. Epub 2021 Jun 21.

Department of Mechanical Engineering and Munich School of Bioengineering, Technical University of Munich, Boltzmannstraße 15, 85748 Garching, Germany; Center for Protein Assemblies, Technical University of Munich, Ernst-Otto-Fischer-Straße 8, 85748 Garching, Germany. Electronic address:

One of the main challenges in the field of drug delivery remains the development of strategies to efficiently transport pharmaceuticals across mucus barriers, which regulate the passage and retention of molecules and particles in all luminal spaces of the body. A thorough understanding of the molecular mechanisms, which govern such selective permeability, is key for achieving efficient translocation of drugs and drug carriers. For this purpose, model systems based on purified mucins can contribute valuable information. Read More

Adv Drug Deliv Rev 2021 Jun 21:113836. Epub 2021 Jun 21.

IRMB, University of Montpellier, INSERM, Montpellier, France; Clinical Immunology and Osteoarticular Disease Therapeutic Unit, Department of Rheumatology, CHU Montpellier, France. Electronic address:

Osteoarthritis (OA) is a common age-related disease that correlates with a high number of senescent cells in joint tissues. Senescence has been reported to be one of the main drivers of OA pathogenesis, in particular via the release of senescence-associated secretory phenotype (SASP) factors. SASP factors are secreted as single molecules and/or packaged within extracellular vesicles (EVs), thereby contributing to senescent phenotype dissemination. Read More

Adv Drug Deliv Rev 2021 Jun 19:113828. Epub 2021 Jun 19.

Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), D-66123 Saarbrücken, Germany; Department of Pharmacy, Saarland University, D-66123 Saarbrücken, Germany. Electronic address:

Current treatment strategies for inflammatory bowel disease (IBD) seek to alleviate the undesirable symptoms of the disorder. Despite the higher specificity of newer generation therapeutics, e.g. Read More

Adv Drug Deliv Rev 2021 Jun 18:113839. Epub 2021 Jun 18.

Department of Bioengineering, California NanoSystems Institute and Center for Minimally Invasive Therapeutics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA; Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, Department of Radiology University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:

Cancer remains one of the leading health burdens worldwide. One of the challenges hindering cancer therapy development is the substantial discrepancies between the existing cancer models and the tumor microenvironment (TME) of human patients. Constructing tumor organoids represents an emerging approach to recapitulate the pathophysiological features of the TME in vitro. Read More

Adv Drug Deliv Rev 2021 Jun 17:113840. Epub 2021 Jun 17.

Manufacturing, Science & Technology, Pharma Supply Chain, GlaxoSmithKline, Ware, UK.

Tablets are the most widely utilized solid oral dosage forms because of the advantages of self-administration, stability, ease of handling, transportation, and good patient compliance. Over time, extensive advances have been made in tableting technology. This review aims to provide an insight about the advances in tablet excipients, manufacturing, analytical techniques and deployment of Quality by Design (QbD). Read More

Adv Drug Deliv Rev 2021 Jun 17:113843. Epub 2021 Jun 17.

Laboratoire MSC Matière et Systèmes Complexes, CNRS UMR 7057, Université de Paris, 750013 Paris.

Extracellular vesicles (EVs) are becoming essential actors in bio-therapeutics, as much for their regenerative or immunomodulatory properties as for their potential as cargo delivery vehicles. To enable the democratization of these EV-based therapies, many challenges remain such as large-scale production which is necessary to reduce costs of treatment. Herein, we review some advanced works on high-yield EV manufacturing. Read More

Adv Drug Deliv Rev 2021 Jun 17:113833. Epub 2021 Jun 17.

Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain. Electronic address:

Imaging of the lymphatic vasculature has gained great attention in various fields, not only because the traditional role of lymphatic vessels as a draining system in the body, but also for their implication in autoimmune diseases, organ transplant, inflammation and cancer. Thus, neolymphangiogenesis, or the generation of new lymphatics is typically an early event in the development of multiple tumor types, particularly in aggressive ones such as malignant melanoma. Still, the understanding of how lymphatic endothelial cells get activated at distal (pre)metastatic niches and their implication in therapy is still unclear. Read More

Adv Drug Deliv Rev 2021 Jun 16:113832. Epub 2021 Jun 16.

Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address:

The past decades have witnessed an increased incidence of neurological disorders (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, ischemic stroke, and epilepsy, which significantly lower patients' life quality and increase the economic and social burden. Recently, nanomedicines composed of imaging and/or therapeutic agents have been explored to diagnose and/or treat NDs due to their enhanced bioavailability, blood-brain barrier (BBB) permeability, and targeting capacity. Intriguingly, dynamic nanoassemblies self-assembled from functional nanoparticles to simultaneously interfere with multiple pathogenic substances and pathological changes, have been regarded as one of the foremost candidates to improve the diagnostic and therapeutic efficacy of NDs. Read More

Adv Drug Deliv Rev 2021 Jun 15:113837. Epub 2021 Jun 15.

ICGM, Univ Montpellier, ENSCM, CNRS, Montpellier, France. Electronic address:

Compared to chemicals that continue to dominate the overall pharmaceutical market, protein therapeutics offer the advantages of higher specificity, greater activity, and reduced toxicity. While nearly all existing therapeutic proteins were developed against soluble or extracellular targets, the ability for proteins to enter cells and target intracellular compartments can significantly broaden their utility for a myriad of exiting targets. Given their physical, chemical, biological instability that could induce adverse effects, and their limited ability to cross cell membranes, delivery systems are required to fully reveal their biological potential. Read More

Adv Drug Deliv Rev 2021 Jun 15:113838. Epub 2021 Jun 15.

Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, de Boelelaan 1117, 1081HV Amsterdam, Netherlands. Electronic address:

Restoring effective anti-tumor immune responses to cure cancer is a promising strategy, but challenged by the intricate crosstalk between tumor and immune cells. While it has long been established that tumor cells acquire traits to escape immune recognition, the involvement of extracellular vesicles (EVs) in blocking immune-activation has only recently been recognized. By assisting cancer cells in relaying immunomodulatory signals in the form of (glyco)proteins, lipids, nucleic acids and metabolic regulators, EVs emerged as potent mediators of immune suppression. Read More

Adv Drug Deliv Rev 2021 Jun 16:113835. Epub 2021 Jun 16.

Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC 28223, USA. Electronic address:

With recent advances in nanotechnology and therapeutic nucleic acids (TNAs), various nucleic acid nanoparticles (NANPs) have demonstrated great promise in diagnostics and therapeutics. However, the full realization of NANPs' potential necessitates the development of a safe, efficient, biocompatible, stable, tissue-specific, and non-immunogenic delivery system. Exosomes, the smallest extracellular vesicles and an endogenous source of nanocarriers, offer these advantages while avoiding complications associated with manufactured agents. Read More

Adv Drug Deliv Rev 2021 Jun 14:113831. Epub 2021 Jun 14.

Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, Faculty of Medicine, RWTH Aachen University, Aachen, Germany; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands; Department of Targeted Therapeutics, University of Twente, Enschede, The Netherlands. Electronic address:

Fibrosis is a common denominator in many pathologies and crucially affects disease progression, drug delivery efficiency and therapy outcome. We here summarize therapeutic and diagnostic strategies for fibrosis targeting in atherosclerosis and cardiac disease, cancer, diabetes, liver diseases and viral infections. We address various anti-fibrotic targets, ranging from cells and genes to metabolites and proteins, primarily focusing on fibrosis-promoting features that are conserved among the different diseases. Read More

Adv Drug Deliv Rev 2021 Jun 14:113830. Epub 2021 Jun 14.

Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center of Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address:

Dynamic nanoassembly-based drug delivery system (DNDDS) has evolved from being a mere curiosity to emerging as a promising strategy for high-performance diagnosis and/or therapy of various diseases. However, dynamic nano-bio interaction between DNDDS and biological systems remains poorly understood, which can be critical for precise spatiotemporal and functional control of DNDDS in vivo. To deepen the understanding for fine control over DNDDS, we aim to explore natural systems as the root of inspiration for researchers from various fields. Read More

Adv Drug Deliv Rev 2021 Jun 10;175:113826. Epub 2021 Jun 10.

Laboratoire de Pharmacie Galénique et de Biopharmacie, Université libre de Bruxelles (ULB), Brussels, Belgium. Electronic address:

This review aims to cement three hot topics in drug delivery: (a) the pre-formulation of new products intended for nose-to-brain delivery; (b) the development of nasal casts for studying the efficacy of potential new nose-to-brain delivery systems at the early of their development (pre-formulation); (c) the use of 3D printing based on a wide variety of materials (transparent, biocompatible, flexible) providing an unprecedented fabrication tool towards personalized medicine by printing nasal cast on-demand based on CT scans of patients. This review intends to show the links between these three subjects. Indeed, the pathway selected to administrate the drug to the brain not only influence the formulation strategies to implement but also the design of the cast, to get the most convincing measures from it. Read More

Adv Drug Deliv Rev 2021 Jun 11;175:113827. Epub 2021 Jun 11.

Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.

Adv Drug Deliv Rev 2021 Jun 7;175:113825. Epub 2021 Jun 7.

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom. Electronic address:

Diabetes affects approximately 450 million adults globally. If not effectively managed, chronic hyperglycaemia causes tissue damage that can develop into fibrosis. Fibrosis leads to end-organ complications, failure of organ systems occurs, which can ultimately cause death. Read More

Adv Drug Deliv Rev 2021 Jun 4;175:113824. Epub 2021 Jun 4.

I3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; CESPU - Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra 1317, 4585-116 Gandra, Portugal. Electronic address:

Colorectal cancer (CRC) is a heterogeneous and molecularly complex disease, associated with high mortality worldwide, exposing the urgent need for novel therapeutic approaches. Their development and translation to the clinic have been hampered, partially due to the absence of reliable cellular models that resemble key features of the human disease. While traditional 2D models are not able to provide consistent and predictive responses about the in vivo efficiency of the formulation, animal models frequently fail to recapitulate cancer progression and to reproduce adverse effects. Read More

Adv Drug Deliv Rev 2021 Jun 3. Epub 2021 Jun 3.

Department of Chemistry, the Chinese University of Hong Kong, Shatin, Hong Kong SAR, China. Electronic address:

Antimicrobial peptides hold promise to supplement small molecules antibiotics and combat the multidrug resistant microbes. There are however technical hurdles towards the clinical applications, largely due to the inherent limitations of peptides including stability, cytotoxicity and bioavailability. Here we review recent studies concerning the delivery and formulation of antimicrobial peptides, by categorizing the different strategies as driven by physical interactions or chemical conjugation reactions, and carriers ranging from inorganic based ones (including gold, silver and silica based solid nanoparticles) to organic ones (including micelle, liposome and hydrogel) are covered. Read More

Adv Drug Deliv Rev 2021 Jun 3;175:113822. Epub 2021 Jun 3.

Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Recently, there have been increasing numbers of publications illustrating the potential of light-based antimicrobial therapies to combat antimicrobial resistance. Several modalities, in particular, which have proven antimicrobial efficacy against a wide range of pathogenic microbes include: photodynamic therapy (PDT), ultraviolet light (UVA, UVB and UVC), and antimicrobial blue light (aBL). Using these techniques, microbial cells can be inactivated rapidly, either by inducing reactive oxygen species that are deleterious to the microbial cells (PDT, aBL and UVA) or by causing irreversible DNA damage via direct absorption (UVB and UVC). Read More

Adv Drug Deliv Rev 2021 Jun 4;175:113823. Epub 2021 Jun 4.

Nanotechnology and Integrated Bioengineering Centre, University of Ulster, Jordanstown Campus, Newtownabbey, Northern Ireland BT37 0QB, UK. Electronic address:

Advancements in technology and material development in recent years has led to significant breakthroughs in the remit of fiber engineering. Conventional methods such as wet spinning, melt spinning, phase separation and template synthesis have been reported to develop fibrous structures for an array of applications. However, these methods have limitations with respect to processing conditions (e. Read More

Adv Drug Deliv Rev 2021 Jun 2;175:113816. Epub 2021 Jun 2.

Université de Paris, AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Centre de recherche sur l'inflammation, Inserm, UMR 1149, Paris, France. Electronic address:

More than eight hundred million people worldwide have chronic liver disease, with two million deaths per year. Recurring liver injury results in fibrogenesis, progressing towards cirrhosis, for which there doesn't exists any cure except liver transplantation. Better understanding of the mechanisms leading to cirrhosis and its complications is needed to develop effective therapies. Read More

Adv Drug Deliv Rev 2021 Jun 2;175:113819. Epub 2021 Jun 2.

AIT Austrian Institute of Technology GmbH, Center for Health and Bioresources, Competence Unit Molecular Diagnostics, Giefinggasse 4, 1210 Vienna, Austria. Electronic address:

Early detection of cancer in order to facilitate timely therapeutic interventions is an unsolved problem in today's clinical diagnostics. Tumors are detected so far mostly after pathological symptoms have emerged (usually already in progressed disease states), within preventive screenings, or occasionally as incidental finding. The emergence of extracellular vesicle (EV) analytics in combination with liquid biopsy sampling opened a plethora of new possibilities for the detection of tumors (and other diseases). Read More

Adv Drug Deliv Rev 2021 Jun 2;175:113820. Epub 2021 Jun 2.

Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Guangzhou 510515, China. Electronic address:

The interactions between inorganic-based nanomaterials (NMs) and biological membranes are among the most important phenomena for developing NM-based therapeutics and resolving nanotoxicology. Herein, we introduce the structural and functional effects of inorganic-based NMs on biological membranes, mainly the plasma membrane and the endomembrane system, with an emphasis on the interface, which involves highly complex networks between NMs and biomolecules (such as membrane proteins and lipids). Significant efforts have been devoted to categorizing and analyzing the interaction mechanisms in terms of the physicochemical characteristics and biological effects of NMs, which can directly or indirectly influence the effects of NMs on membranes. Read More

Adv Drug Deliv Rev 2021 Jun 1. Epub 2021 Jun 1.

Department of Biomedical Engineering, National University of Singapore, Singapore; The N.1 Institute for Health, National University of Singapore, Singapore. Electronic address:

Based on our exponentially increasing knowledge of stromal heterogeneity from advances in single-cell technologies, the notion that stromal cell types exist as a spectrum of unique subpopulations that have specific functions and spatial distributions in the tumor microenvironment has significant impact on tumor modeling for drug development and personalized drug testing. In this Review, we discuss the importance of incorporating stromal heterogeneity and tumor architecture, and propose an overall approach to guide the reconstruction of stromal heterogeneity in vitro for tumor modeling. These next-generation tumor models may support the development of more precise drugs targeting specific stromal cell subpopulations, as well as enable improved recapitulation of patient tumors in vitro for personalized drug testing. Read More

Adv Drug Deliv Rev 2021 Jun 1. Epub 2021 Jun 1.

CINBIO, Universidade de Vigo, Immunology Group, Vigo, Spain; Galicia Sur Health Research Institute (IIS-GS), Hospital Alvaro Cunqueiro, Vigo, Spain.

Emerging evidences show that innate immune cells can display changes in their functional programs after infection or vaccination, which lead to immunomodulation (increased or reduced responsiveness) upon secondary activation to the same stimuli or even to a different one. Innate cells acquire features of immunological memory, nowadays using the new term of "trained immunity" or "innate immune memory", which is different from the specific memory immune response elicited by B and T lymphocytes. The review focused on the concept of trained immunity, mostly on myeloid cells. Read More

Adv Drug Deliv Rev 2021 May 28. Epub 2021 May 28.

Université de Paris, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, F-75014 Paris, France; GHU Paris Psychiatrie et Neurosciences, Hôpital Sainte Anne, F-75014 Paris, France. Electronic address:

Extracellular Vesicles (EVs) are released during various pathophysiological processes and reflect the state of their cell of origin. Once released, they can propagate through biological fluids, target cells, deliver their content and elicit functional responses. These specific features would allow their harnessing as biomarkers, drug nano-vehicles and therapeutic intrinsic modulators. Read More

Adv Drug Deliv Rev 2021 May 29;175:113803. Epub 2021 May 29.

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Electronic address:

Imidazoquinoline derivatives (IMDs) and related compounds function as synthetic agonists of Toll-like receptors 7 and 8 (TLR7/8) and one is FDA approved for topical antiviral and skin cancer treatments. Nevertheless, these innate immune system-activating drugs have potentially much broader therapeutic utility; they have been pursued as antitumor immunomodulatory agents and more recently as candidate vaccine adjuvants for cancer and infectious disease. The broad expression profiles of TLR7/8, poor pharmacokinetic properties of IMDs, and toxicities associated with systemic administration, however, are formidable barriers to successful clinical translation. Read More

Adv Drug Deliv Rev 2021 May 27;175:113814. Epub 2021 May 27.

Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland. Electronic address:

Overcoming the gastrointestinal (GI) barriers is a formidable challenge in the oral delivery of active macromolecules such as peptide- and protein- based drugs. In the past four decades, a plethora of formulation strategies ranging from permeation enhancers, nanosized carriers, and chemical modifications of the drug's structure has been investigated to increase the oral absorption of these macromolecular compounds. However, only limited successes have been achieved so far, with the bioavailability of marketed oral peptide drugs remaining generally very low. Read More

Adv Drug Deliv Rev 2021 May 24;175:113809. Epub 2021 May 24.

Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, 92296 Châtenay-Malabry, France. Electronic address:

Thanks to their abilities to modulate the expression of virtually any genes, RNA therapeutics have attracted considerable research efforts. Among the strategies focusing on nucleic acid gene inhibitors, antisense oligonucleotides and small interfering RNAs have reached advanced clinical trial phases with several of them having recently been marketed. These successes were obtained by overcoming stability and cellular delivery issues using either chemically modified nucleic acids or nanoparticles. Read More

Adv Drug Deliv Rev 2021 May 23;175:113810. Epub 2021 May 23.

University of Liege, Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines (CIRM), B36 Tower 4, 2nd floor, Avenue Hippocrate 15, 4000 Liège, Belgium.

In recent years, fused deposition modeling has become one of the most used three-dimensional printing technologies in the pharmaceutical field. The production of personalized dosage forms for individualized therapy and the modification of the drug release profile by the elaboration of complex geometries make fused deposition modeling a promising tool for small-scale production. However, fused deposition modeling has a considerable number of challenges to overcome. Read More