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Adv Drug Deliv Rev 2020 Jul 11. Epub 2020 Jul 11.

RTI International, Research Triangle Park, NC, USA; UNC Catalyst for Rare Disease, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC, USA. Electronic address:

Ideally, inhaled therapy is driven by the needs of specific disease management. Lung biology interfaces with inhaler performance to allow optimal delivery of therapeutic agent for disease treatment. Inhalation aerosol products consist of the therapeutic agent, formulation, and device. Read More

Adv Drug Deliv Rev 2020 Jul 10. Epub 2020 Jul 10.

Laboratory of Precision NanoMedicine, School of Molecular Cell Biology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel-Aviv, Israel; Department of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel; Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv, Israel; Cancer Biology Research Center, Tel Aviv University, Tel Aviv, Israel. Electronic address:

CRISPR/Cas systems (clustered regularly interspaced short palindromic repeats) have emerged as powerful tools to manipulate the genome for both research and therapeutic purposes. However, the clinical use of this system is hindered by multiple challenges, such as the rate of off-target effects, editing efficiency, the efficacy of HDR, immunogenicity, as well as development of efficient and safe delivery vehicles that can carry these compounds. Tremendous efforts are being conducted to overcome these challenges, including the discovery and engineering of more precise and efficacious Cas nucleases. Read More

Adv Drug Deliv Rev 2020 Jul 10. Epub 2020 Jul 10.

Laboratory of Theranostics, Faculty of Pharma-Science, Teikyo University, Tokyo, Japan. Electronic address:

Microbubbles with diagnostic ultrasound have had a long history of use in the medical field. In recent years, the therapeutic application of the combination of microbubbles and ultrasound, called sonoporation, has received increased attention as microbubble oscillation or collapse close to various barriers in the body was recognized to potentially open those barriers, increasing drug transport across them. In this review, we aimed to describe the development of lipid-stabilized microbubbles equipped with functions, such as long circulation and drug loading, and the therapeutic application of sonoporation for tumor-targeted therapy, brain-targeted therapy, and immunotherapy. Read More

Adv Drug Deliv Rev 2020 Jul 8. Epub 2020 Jul 8.

Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1, Kashiwanoha, Kashiwa 277-8577,Japan. Electronic address:

Many animal experiments performed worldwide have proven EPR effects However, it is hard to say that the EPR effect works in clinical practice. In the case of hematological malignancies, the administered anticancer agents (ACA) can physically interact with the malignant cells, making it easier to reflect in vitro data. In solid tumors, however, the extravasated ACAs must diffuse evenly within the whole tumor mass. Read More

Adv Drug Deliv Rev 2020 Jul 7. Epub 2020 Jul 7.

Strathclyde Institute of Pharmacy and Biomedical Sciences, 161 Cathedral St, The University of Strathclyde, Glasgow G4 0RE, Scotland, United Kingdom. Electronic address:

Liposomes are well recognised as effective drug delivery systems, with a range of products approved, including follow on generic products. Current manufacturing processes used to produce liposomes are generally complex multi-batch processes. Furthermore, liposome preparation processes adopted in the laboratory setting do not offer easy translation to large scale production, which may delay the development and adoption of new liposomal systems. Read More

Adv Drug Deliv Rev 2020 Jul 7. Epub 2020 Jul 7.

Graduate School of Pharmaceutical Science, Chiba University, Japan. Electronic address:

Messenger RNA and small interfering RNA are attractive modalities for curing diseases by complementation or knock-down of proteins. For success of these RNAs, a drug delivery system (DDS) is required to control a pharmacokinetics, to enhance cellular uptake, to overcome biological membranes, and to release the cargo into the cytoplasm. Based on past research, developing nanoparticles that are neutrally charged have been the mainstream of their development. Read More

Adv Drug Deliv Rev 2020 Jul 6. Epub 2020 Jul 6.

INSERM, Research Center for Respiratory Diseases, U1100, Tours, France; University of Tours, Tours, France. Electronic address:

Nonclinical studies are fundamental for the development of inhaled drugs, as for any drug product, and for successful translation to clinical practice. They include in silico, in vitro, ex vivo and in vivo studies and are intended to provide a comprehensive understanding of the inhaled drug beneficial and detrimental effects. To date, animal models cannot be circumvented during drug development programs, acting as surrogates of humans to predict inhaled drug response, fate and toxicity. Read More

Adv Drug Deliv Rev 2020 Jul 3. Epub 2020 Jul 3.

Department of Medicine, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy; European Center for Brain Research/IRCCS Santa Lucia Foundation, Via del Fosso di Fiorano 64, 00143 Rome, Italy. Electronic address:

Endogenous bioactive lipids are part of a complex network that modulates a plethora of cellular and molecular processes involved in health and disease, of which inflammation represents one of the most prominent examples. Inflammation serves as a well-conserved defence mechanism, triggered in the event of chemical, mechanical or microbial damage, that is meant to eradicate the source of damage and restore tissue function. However, excessive inflammatory signals, or impairment of pro-resolving/anti-inflammatory pathways leads to chronic inflammation, which is a hallmark of chronic pathologies. Read More

Adv Drug Deliv Rev 2020 Jul 1. Epub 2020 Jul 1.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA; Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA; McKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, TX 78712, USA; Departments of Pediatrics and Surgery, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA. Electronic address:

The widespread development of nanocarriers to deliver chemotherapeutics to specific tumor sites has been motivated by the lack of selective targeting during chemotherapy inducing serious side effects and low therapeutic efficacy. The utmost challenge in targeted cancer therapies is the ineffective drug delivery system, in which the drug-loaded nanocarriers are hindered by multiple complex biological barriers that compromise the therapeutic efficacy. Despite considerable progress engineering novel nanoplatforms for the delivery of chemotherapeutics, there has been limited success in a clinical setting. Read More

Adv Drug Deliv Rev 2020 Jul 2. Epub 2020 Jul 2.

Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.

Hereditary genetic disorders, cancer, and infectious diseases of the liver affect millions of people around the globe and are a major public health burden. Most contemporary treatments offer limited relief as they generally aim to alleviate disease symptoms. Targeting the root cause of diseases originating in the liver by regulating malfunctioning genes with nucleic acid-based drugs holds great promise as a therapeutic approach. Read More

Adv Drug Deliv Rev 2020 Jun 30. Epub 2020 Jun 30.

Translational Liver Research, Department of Medical Cell BioPhysics, Faculty of Science and Technology, Technical Medical Center, University of Twente, Enschede 7500 AE, the Netherlands. Electronic address:

The liver is the key organ involved in lipid metabolism and transport. Excessive lipid accumulation due to dysregulated lipid metabolism predisposes the liver to steatosis, cirrhosis, and hepatocellular carcinoma. Lipids are generally compartmentalized in specialized organelles called lipid droplets that enable cells to store and release lipids in a regulated manner. Read More

Adv Drug Deliv Rev 2020 Jun 29. Epub 2020 Jun 29.

Department of Chemistry, University of Massachusetts Amherst, 710 N. Pleasant St., Amherst, MA 01003, USA. Electronic address:

Inorganic nanoparticles provide multipurpose platforms for a broad range of delivery applications. Intrinsic nanoscopic properties provide access to unique magnetic and optical properties. Equally importantly, the structural and functional diversity of gold, silica, iron oxide, and lanthanide-based nanocarriers provide unrivalled control of nanostructural properties for effective transport of therapeutic cargos, overcoming biobarriers on the cellular and organismal level. Read More

Adv Drug Deliv Rev 2020 Jun 27. Epub 2020 Jun 27.

Ocular Gene Therapy Core, National Eye Institute, National Institutes of Health, 6 Center Drive, Room 306, Bethesda, MD 20892, USA. Electronic address:

A variety of inherited or multifactorial ocular diseases call for novel treatment paradigms. The newly developed genome editing technology, CRISPR, has shown great promise in treating these diseases, but delivery of the CRISPR/Cas components to target ocular tissues and cells requires appropriate use of vectors and routes of administration to ensure safety, efficacy and specificity. Although adeno-associated viral (AAV) vectors are thus far the most commonly used tool for ocular gene delivery, sustained expression of CRISPR/Cas components may cause immune reactions and an increased risk of off-target editing. Read More

Adv Drug Deliv Rev 2020 Jun 27. Epub 2020 Jun 27.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Centre, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA; Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore 21218, USA; Department of Mechanical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore 21218, USA. Electronic address:

Significant research and preclinical investment in cancer nanomedicine has produced several products, which have improved cancer care. Nevertheless, there exists a perception that cancer nanomedicine 'has not lived up to its promise' because the number of approved products and their clinical performance are modest. Many of these analyses do not consider the long clinical history and many clinical products developed from iron oxide nanoparticles. Read More

Adv Drug Deliv Rev 2020 Jun 27. Epub 2020 Jun 27.

Department of Bioengineering, University of California-San Diego, La Jolla, CA 92093, United States; Department of NanoEngineering, University of California-San Diego, La Jolla, CA 92093, United States; Department of Radiology, University of California-San Diego, La Jolla, CA 92093, United States; Moores Cancer Center, University of California-San Diego, La Jolla, CA 92093, United States; Center for Nano-ImmunoEngineering, University of California-San Diego, La Jolla, CA 92093, United States. Electronic address:

Viral nanoparticles (VNPs) encompass a diverse array of naturally occurring nanomaterials derived from plant viruses, bacteriophages, and mammalian viruses. The application and development of VNPs and their genome-free versions, the virus-like particles (VLPs), for nanomedicine is a rapidly growing. VLPs can encapsulate a wide range of active ingredients as well as be genetically or chemically conjugated to targeting ligands to achieve tissue specificity. Read More

Adv Drug Deliv Rev 2020 Jun 26. Epub 2020 Jun 26.

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.

Vaccines are one of the most powerful technologies supporting public health. The adaptive immune response induced by immunization arises following appropriate activation and differentiation of T and B cells in lymph nodes. Among many parameters impacting the resulting immune response, the presence of antigen and inflammatory cues for an appropriate temporal duration within the lymph nodes, and further within appropriate subcompartments of the lymph nodes- the right timing and location- play a critical role in shaping cellular and humoral immunity. Read More

Adv Drug Deliv Rev 2020 Jun 25. Epub 2020 Jun 25.

Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA; Department of Oncology, Radiotherapy and Plastic Surgery, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. Electronic address:

The liposomes have continued to be well-recognized as an important nano-sized drug delivery system with attractive properties, such a characteristic bilayer structure assembling the cellular membrane, easy-to-prepare and high bio-compatibility. Extensive effort has been devoted to the development of liposome-based drug delivery systems during the past few decades. Many drug candidates have been encapsulated in liposomes and investigated for reduced toxicity and extended duration of therapeutic effect. Read More

Adv Drug Deliv Rev 2020 Jun 25. Epub 2020 Jun 25.

University of Sydney, Sydney, Australia.

Conventional in vitro tests to assess the aerodynamic particle size distribution (APSD) from inhaler devices use simple right-angle inlets ("mouth-throats", MTs) to cascade impactors, and air is drawn through the system at a fixed flow for a fixed time. Since this arrangement differs substantially from both human oropharyngeal airway anatomy and the patterns of air flow when patients use inhalers, the ability of in vitro tests to predict in vivo deposition of pharmaceutical aerosols has been limited. MTs that mimic the human anatomy, coupled with simulated breathing patterns, have yielded estimates of lung dose from in vitro data that closely match those from in vivo gamma scintigraphic or pharmacokinetic studies. Read More

Adv Drug Deliv Rev 2020 Jun 24. Epub 2020 Jun 24.

Purdue University, 206 S. Martin Jischke Drive, West Lafayette, IN 47907, United States of America.

Drug delivery systems are developed to maximize drug efficacy and minimize side effects. As drug delivery technologies improve, the drug becomes safer and more comfortable for patients to use. During the last seven decades, extraordinary progress has been made in drug delivery technologies, such as systems for long-term delivery for months and years, localized delivery, and targeted delivery. Read More

Adv Drug Deliv Rev 2020 Jun 24. Epub 2020 Jun 24.

John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA. Electronic address:

Physically triggered systems hold promise for improving drug delivery by enhancing the controllability of drug accumulation and release, lowering non-specific toxicity, and facilitating clinical translation. Several external physical stimuli including ultrasound, light, electric fields and magnetic fields have been used to control drug delivery and they share some common features such as spatial targeting, spatiotemporal control, and minimal invasiveness. At the same time, they possess several distinctive features in terms of interactions with biological entities and/or the extent of stimulus response. Read More

Adv Drug Deliv Rev 2020 Jun 24. Epub 2020 Jun 24.

Department of Pharmaceutical Health Chemistry, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8505, Japan. Electronic address:

Noninvasive transdermal drug delivery (NTDD) offers an exciting new method of administration relative to conventional routes, but is associated with some challenges. Liposomes are capable of encapsulating transdermally-unfavorable drugs. However, the horny layer of skin is a significant barrier that limits efficient transdermal delivery of liposomes. Read More

Adv Drug Deliv Rev 2020 Jun 23. Epub 2020 Jun 23.

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address:

To develop new therapeutics involves the interaction of multiple disciplines to yield safe, functional devices and formulations. Regardless of drug function and potency, administration with controlled timing, dosing, and targeting is required to properly treat or regulate health and disease. Delivery approaches can be optimized through advances in materials science, clinical testing, and basic biology and immunology. Read More

Adv Drug Deliv Rev 2020 Jun 23. Epub 2020 Jun 23.

Department of Biomedical Engineering, Yale University, New Haven, CT 06511, United States of America; Department of Chemical & Environmental Engineering, Yale University, New Haven, CT 06511, United States of America; Department of Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT 06510, United States of America; Department of Dermatology, Yale School of Medicine, New Haven, CT 06510, United States of America. Electronic address:

Polymeric vehicles are versatile tools for therapeutic gene delivery. Many polymers-when assembled with nucleic acids into vehicles-can protect the cargo from degradation and clearance in vivo, and facilitate its transport into intracellular compartments. Design options in polymer synthesis yield a comprehensive range of molecules and resulting vehicle formulations. Read More

Adv Drug Deliv Rev 2020 Jun 21. Epub 2020 Jun 21.

Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address:

Near-infrared (NIR) light possesses many suitable optophysical properties for medical imaging including low autofluorescence, deep tissue penetration, and minimal light scattering, which together allow for high-resolution imaging of biological tissue. NIR imaging has proven to be a noninvasive and effective real-time imaging methodology that provides a high signal-to-background ratio compared to other potential optical imaging modalities. In response to this, the use of NIR imaging has been extensively explored in the field of immunotherapy. Read More

Adv Drug Deliv Rev 2020 Jun 21. Epub 2020 Jun 21.

Department of Systems Pharmacology and Translational Therapeutics, Center for Targeted Therapeutics and Translational Nanomedicine of the Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States of America. Electronic address:

The bloodstream is the main transporting pathway for drug delivery systems (DDS) from the site of administration to the intended site of action. In many cases, components of the vascular system represent therapeutic targets. Endothelial cells, which line the luminal surface of the vasculature, play a tripartite role of the key target, barrier, or victim of nanomedicines in the bloodstream. Read More

Adv Drug Deliv Rev 2020 Jun 20. Epub 2020 Jun 20.

Faculty of Pharmaceutical Sciences, University of British Columbia, 2405 Wesbrook Mall, Vancouver, British Columbia V6T 1Z3, Canada. Electronic address:

Liver diseases such as hepatitis, cirrhosis, and hepatocellular carcinoma are global health problems accounting for approximately 800 million cases and over 2 million deaths per year worldwide. Major drawbacks of standard pharmacological therapies are the inability to deliver a sufficient concentration of a therapeutic agent to the diseased liver, and nonspecific drug delivery leading to undesirable systemic side effects. Additionally, depending on the specific liver disease, drug delivery to a subset of liver cells is required. Read More

Adv Drug Deliv Rev 2020 Jun 19. Epub 2020 Jun 19.

Institute for Integrated Cell-Material Sciences, Kyoto University, Yoshidaushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan; Graduate School of Pharmaceutical Sciences(2), Kyoto University, Yoshidaushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address:

Drug delivery system is defined as a system or technology to achieve optimum therapeutic effects of drugs through precise control of their movements in the body. In order to optimize function of drug delivery systems aiming at targeting, their whole-body distribution profiles should be systematically evaluated and analyzed, where pharmacokinetic analysis based on the clearance concepts plays important role. Organ perfusion experiments combined with statistical moment analysis further supply detailed information on drug disposition at organ and cellular levels. Read More

Adv Drug Deliv Rev 2020 Jun 14. Epub 2020 Jun 14.

Department of Microbiology, Graduate School of Medical Sciences, Kumamoto 860-8556, Japan; BioDynamics Research Foundation, Kumamoto 862-0954, Japan. Electronic address:

The enhanced permeability and retention (EPR) effect is a unique phenomenon of solid tumors that is related to their particular anatomical and pathophysiological characteristics, e.g. defective vascular architecture; large gaps between endothelial cells in blood vessels; abundant vascular mediators such as bradykinin, nitric oxide, carbon monoxide, and vascular endothelial growth factor; and impaired lymphatic recovery. Read More

Adv Drug Deliv Rev 2020 Jun 14. Epub 2020 Jun 14.

Institute for Molecular Cardiovascular Research, University Hospital RWTH Aachen, Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; School for Cardiovascular Diseases, Maastricht University, Universiteitssingel 50, Maastricht, The Netherlands. Electronic address:

Lipids are ubiquitous in the human organism and play essential roles as components of cell membranes and hormones, for energy storage or as mediators of cell signaling pathways. As crucial mediators of the human metabolism, lipids are also involved in metabolic diseases, cardiovascular and renal diseases, cancer and/or hepatological and neurological disorders. With rapidly growing evidence supporting the impact of lipids on both the genesis and progression of these diseases as well as patient wellbeing, the characterization of the human lipidome has gained high interest and importance in life sciences and clinical diagnostics within the last 15 years. Read More

Adv Drug Deliv Rev 2020 Jun 15. Epub 2020 Jun 15.

CSIRO Manufacturing, Research Way, Clayton 3168, Victoria, Australia. Electronic address:

A broad range of medical devices initiate an immune reaction known as the foreign body response (FBR) upon implantation. Here, collagen deposition at the surface of the implant occurs as a result of the FBR, ultimately leading to fibrous encapsulation and, in many cases, reduced function or failure of the device. Despite significant efforts, the prevention of fibrotic encapsulation has not been realized at this point in time. Read More

Adv Drug Deliv Rev 2020 Jun 11. Epub 2020 Jun 11.

Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA. Electronic address:

Micro and nanoscale drug carriers must navigate through a plethora of dynamic biological systems prior to reaching their tissue or disease targets. The biological obstacles to drug delivery come in many forms and include tissue barriers, mucus and bacterial biofilm hydrogels, the immune system, and cellular uptake and intracellular trafficking. The biointerface of drug carriers influences how these carriers navigate and overcome biological barriers for successful drug delivery. Read More

Adv Drug Deliv Rev 2020 Jun 8. Epub 2020 Jun 8.

Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:

Reactive oxygen species (ROS) play important roles in cell signaling and tissue homeostasis, in which the level of ROS is critical through the equilibrium between ROS generating and eliminating events. A disruption of the balance leads to disease development either by a surplus or a dearth of ROS, which requires ROS-modulating strategies to overturn the defect for disease treatment. Over the past decade, there have been tremendous advances in nanomedicine centering ROS generation and/or elimination as major mechanisms to treat a variety of diseases. Read More

Adv Drug Deliv Rev 2020 Jun 8. Epub 2020 Jun 8.

Genevant Sciences Corp., 155 - 887 Great Northern Way, Vancouver, British Columbia V5T 4T5, Canada. Electronic address:

Nucleic Acid (NA) based therapeutics are poised to disrupt modern medicine and augment traditional pharmaceutics in a meaningful way. However, a key challenge to advancing NA therapies into the clinical setting and on to the market is the safe and effective delivery to the target tissue and cell. Lipid Nanoparticles (LNP) have been extensively investigated and are currently the most advanced vector for the delivery of NA drugs, as evidenced by the approval of Onpattro for treatment of Amyloidosis in the US and EU in 2018. Read More

Adv Drug Deliv Rev 2020 Jun 8. Epub 2020 Jun 8.

Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA; Broad Institute of Harvard and MIT, 7 Cambridge Center, MA 02142, USA; Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA. Electronic address:

The process of aging influences every bodily organ and tissue, and those with rapid epithelial cell turnover, are particularly affected. The most visible of these, however, is the skin (including the epidermis), the largest human organ that provides a barrier to external insults, structure to the body and its movements, facilitates thermoregulation, harbors immune cells, and incorporates sensory neurons (including mechanoreceptors, nociceptors, and thermoreceptors). Skin aging has traditionally been categorized into intrinsic and extrinsic, with the latter nearly exclusively restricted to "photoaging," (i. Read More

Adv Drug Deliv Rev 2020 Jun 9. Epub 2020 Jun 9.

Department of Immunotherapeutics and Biotechnology, Department of Pharmacy Practice, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Abilene, TX, USA.

Nanoparticles can provide effective control of the release rate and tissue distribution of their drug payload, leading to major pharmacokinetic and pharmacodynamic changes vis-à-vis the conventional administration of free drugs. In the last two decades, we have witnessed major progress in the synthesis and characterization of engineered nanoparticles for imaging and treatment of cancers, resulting in the approval for clinical use of several products and in new and promising approaches. Despite these advances, clinical applications of nanoparticle-based therapeutic and imaging agents remain limited due to biological, immunological, and translational barriers. Read More

Adv Drug Deliv Rev 2020 Jun 5. Epub 2020 Jun 5.

Advanced Drug Delivery Group, School of Pharmacy, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address:

The clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) system has significant therapeutic potentials for lung congenital diseases such as cystic fibrosis, as well as other pulmonary disorders like lung cancer and obstructive diseases. Local administration of CRISPR/Cas9 therapeutics through inhalation can achieve high drug concentration and minimise systemic exposure. While the field is advancing with better understanding on the biological functions achieved by CRISPR/Cas9 systems, the lack of progress in inhalation formulation and delivery of the molecule may impede their clinical translation efficiently. Read More

Adv Drug Deliv Rev 2020 Jun 5. Epub 2020 Jun 5.

Department of Bioengineering, University of Washington, Seattle, WA 98195, United States of America.

Adv Drug Deliv Rev 2020 Jun 6. Epub 2020 Jun 6.

Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.

It is generally known that the lymph nodes (LNs) are important tissues in cancer immunotherapy. Therefore, delivering immune functional compounds to LNs is a useful strategy for enhancing cancer immunotherapy. Lipid-based nanocarriers have been widely used as delivery systems that target LNs, but lipid nanoparticle (LNP) technology has recently attracted increased interest. Read More

Adv Drug Deliv Rev 2020 Jun 1. Epub 2020 Jun 1.

John A. Paulson School of Engineering & Applied Sciences Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138, United States of America. Electronic address:

Nanoparticles offer new opportunities for the treatment of skin diseases. The barrier function of the skin poses a significant challenge for nanoparticles to permeate into the tissue, although the barrier is partially compromised in case of injury or inflammation, as in the case of skin cancer. This may facilitate the penetration of nanoparticles. Read More

Adv Drug Deliv Rev 2020 May 30. Epub 2020 May 30.

Wits/SAMRC Antiviral Gene Therapy Research Unit, Department of Molecular Medicine and Haematology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, South Africa. Electronic address:

Chronic infection with the hepatitis B virus (HBV) remains a significant worldwide medical problem. While diseases caused by HIV infection, tuberculosis and malaria are on the decline, new cases of chronic hepatitis B are on the rise. Because often fatal complications of cirrhosis and hepatocellular carcinoma are associated with chronic hepatitis B, the need for a cure is as urgent as ever. Read More

Adv Drug Deliv Rev 2020 May 30. Epub 2020 May 30.

Institute for Diabetes and Obesity, Helmholtz Zentrum München, Neuherberg, Germany; Helmholtz Diabetes Center & German Center for Diabetes Research (DZD), Helmholtz Zentrum München, Neuherberg, Germany; Department of Pharmacology, Experimental Therapy and Toxicology, Eberhard Institute of Experimental and Clinical Pharmacology and Pharmacogenomics, Karls University Hospitals and Clinics, 72076 Tübingen, Germany.

Derangements in triglyceride and cholesterol metabolism (dyslipidemia) are major risk factors for the development of cardiovascular diseases in obese and type-2 diabetic (T2D) patients. An emerging class of glucagon-like peptide-1 (GLP-1) analogues and next generation peptide dual-agonists such as GLP-1/glucagon or GLP-1/GIP could provide effective therapeutic options for T2D patients. In addition to their role in glucose and energy homeostasis, GLP-1, GIP and glucagon serve as regulators of lipid metabolism. Read More

Adv Drug Deliv Rev 2020 May 29. Epub 2020 May 29.

Department of Pharmacy and Pharmacology, University of Bath, BA2 7AY, UK.

In its 33 years, ADDR has published regularly on the po5tential of oral delivery of biologics especially peptides and proteins. In the intervening period, analysis of the preclinical and clinical trial failures of many purported platform technologies has led to reflection on the true status of the field and reigning in of expectations. Oral formulations of semaglutide, octreotide, and salmon calcitonin have completed Phase III trials, with oral semaglutide being approved by the FDA in 2019. Read More

Adv Drug Deliv Rev 2020 May 28. Epub 2020 May 28.

Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States. Electronic address:

Various bioactive ingredients have been extracted from Chinese herbal medicines (CHMs) that affect tumor progression and metastasis. To further understand the mechanisms of CHMs in cancer therapy, this article summarizes the effects of five categories of CHMs and their active ingredients on tumor cells and the tumor microenvironment. Despite their treatment potential, the undesirable physicochemical properties (poor permeability, instability, high hydrophilicity or hydrophobicity, toxicity) and unwanted pharmacokinetic profiles (short half-life in blood and low bioavailability) restrict clinical studies of CHMs. Read More

Adv Drug Deliv Rev 2020 May 27. Epub 2020 May 27.

Merck & Co., Inc, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA. Electronic address:

Despite the increasing trend towards subcutaneous delivery of monoclonal antibodies, factors influencing the subcutaneous bioavailability of these molecules remain poorly understood. To address critical knowledge gaps and issues during development of subcutaneous dosage forms for monoclonal antibodies, the Subcutaneous Drug Delivery and Development Consortium was convened in 2018 as a pre-competitive collaboration of recognized industry experts. One of the Consortium's eight problem statements highlights the challenges of predicting human bioavailability of subcutaneously administered monoclonal antibodies due to a lack of reliable in vitro and preclinical in vivo predictive models. Read More

Adv Drug Deliv Rev 2020 May 22. Epub 2020 May 22.

Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address:

Cancer is one of the most severe disease burdens in modern times, with an estimated increase in the number of patients diagnosed globally from 18.1 million in 2018 to 23.6 million in 2030. Read More

Adv Drug Deliv Rev 2020 May 11. Epub 2020 May 11.

Translational Laboratories in Genetic Medicine, Agency for Science, Technology and Research (A*STAR), Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address:

Lipids are hydrophobic and amphiphilic molecules involved in diverse functions such as membrane structure, energy metabolism, immunity, and signaling. However, altered intra-cellular lipid levels or composition can lead to metabolic and inflammatory dysfunction, as well as lipotoxicity. Thus, intra-cellular lipid homeostasis is tightly regulated by multiple mechanisms. Read More

Adv Drug Deliv Rev 2020 May 14. Epub 2020 May 14.

Respira Therapeutics, Inc., 1828 El Camino Real #806, Burlingame, CA 94010, USA. Electronic address:

This review provides an assessment of post-inhalation cough with therapeutic aerosols. Factors that increase cough may be mitigated through design of the drug, formulation, and device. The incidence of cough is typically less than 5% for drugs with a nominal dose less than 1 mg, including asthma and COPD therapeutics. Read More

Adv Drug Deliv Rev 2020 May 13. Epub 2020 May 13.

Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics (IDUN), Department of Health Technology, Technical University of Denmark, Denmark. Electronic address:

Orally ingestible medical devices provide significant advancement for diagnosis and treatment of gastrointestinal (GI) tract-related conditions. From micro- to macroscale devices, with designs ranging from very simple to complex, these medical devices can be used for site-directed drug delivery in the GI tract, real-time imaging and sensing of gut biomarkers. Equipped with uni-direction release, or self-propulsion, or origami design, these microdevices are breaking the barriers associated with drug delivery, including biologics, across the GI tract. Read More

Adv Drug Deliv Rev 2020 May 13. Epub 2020 May 13.

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address:

Genome-editing systems based on clustered, regularly interspaced, short palindromic repeat (CRISPR)/associated protein (CRISPR/Cas), are emerging as a revolutionary technology for the treatment of various genetic diseases. To date, the delivery of genome-editing biomacromolecules by viral or non-viral vectors have been proposed as new therapeutic options for lung genetic disorders, such as cystic fibrosis (CF) and α-1 antitrypsin deficiency (AATD), and it has been accepted that these delivery vectors can introduce CRISPR/Cas9 machineries into target cells or tissues in vitro, ex vivo and in vivo. However, the efficient local or systemic delivery of CRISPR/Cas9 elements to the lung, enabled by either viral or by non-viral carriers, still remains elusive. Read More

Adv Drug Deliv Rev 2020 May 7. Epub 2020 May 7.

S. M. Discovery Group Inc., Denver, CO, USA; S. M. Discovery Group Ltd., Durham, UK.

Considering the multifaceted protective and homeostatic roles of the complement system, many consequences arise when drug carriers, and particulate pharmaceutical formulations clash with complement proteins, and trigger complement cascade. Complement activation may induce formulation destabilization, promote opsonization, and affect biological and therapeutic performance of pharmaceutical nano- and micro-particles. In some cases, complement activation is beneficial, where complement may play a role in prophylactic protection, whereas uncontrolled complement activation is deleterious, and contributes to disease progression. Read More