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Advanced Drug Delivery Reviews

Ella N Hoogenboezem, Craig L Duvall
Serum albumin, a natural ligand carrier that is highly concentrated and long-circulating in the blood, has shown remarkable promise as a carrier for anti-cancer agents. Albumin is able to prolong the circulation half-life of otherwise rapidly cleared drugs and, importantly, promote their accumulation within tumors. The applications for using albumin as a cancer drug carrier are broad and include both traditional cancer chemotherapeutics and new classes of biologics. Strategies for leveraging albumin for drug delivery can be classified broadly into exogenous and in situ binding formulations that utilize covalent attachment, non-covalent association, or encapsulation in albumin-based nanoparticles...
July 13, 2018: Advanced Drug Delivery Reviews
Guojun Chen, Yuyuan Wang, Ruosen Xie, Shaoqin Gong
Polymeric unimolecular nanoparticles (NPs) exhibiting a core-shell structure and formed by a single multi-arm molecule containing only covalent bonds have attracted increasing attention for numerous biomedical applications. This unique single-molecular architecture provides the unimolecular NP with superior stability both in vitro and in vivo, a high drug loading capacity, as well as versatile surface chemistry, thereby making it a desirable nanoplatform for therapeutic and diagnostic applications. In this review, we surveyed the architecture of various types of polymeric unimolecular NPs, including water-dispersible unimolecular micelles and water-soluble unimolecular NPs used for the delivery of hydrophobic and hydrophilic agents, respectively, as well as their diverse biomedical applications...
July 12, 2018: Advanced Drug Delivery Reviews
Susanne K Golombek, Jan-Niklas May, Benjamin Theek, Lia Appold, Natascha Drude, Fabian Kiessling, Twan Lammers
The tumor accumulation of nanomedicines relies on the enhanced permeability and retention (EPR) effect. In the last 5-10 years, it has been increasingly recognized that there is a large inter- and intra-individual heterogeneity in EPR-mediated tumor targeting, explaining the heterogeneous outcomes of clinical trials in which nanomedicine formulations have been evaluated. To address this heterogeneity, as in other areas of oncology drug development, we have to move away from a one-size-fits-all tumor targeting approach, towards methods that can be employed to individualize and improve nanomedicine treatments...
July 12, 2018: Advanced Drug Delivery Reviews
Minzhi Yu, Mason M Benjamin, Santhanakrishnan Srinivasan, Emily E Morin, Ekaterina I Shishatskaya, Steven P Schwendeman, Anna Schwendeman
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) belong to an important therapeutic class for treatment of type 2 diabetes. Six GLP-1 RAs, each utilizing a unique drug delivery strategy, are now approved by the Food and Drug Administration (FDA) and additional, novel GLP-1 RAs are still under development, making for a crowded marketplace and fierce competition among the manufacturers of these products. As rapid elimination is a major challenge for clinical application of GLP-1 RAs, various half-life extension strategies have been successfully employed including sequential modification, attachment of fatty-acid to peptide, fusion with human serum albumin, fusion with the fragment crystallizable (Fc) region of a monoclonal antibody, sustained drug delivery systems, and PEGylation...
July 12, 2018: Advanced Drug Delivery Reviews
Xinxin Fu, Jingxuan Cai, Xiang Zhang, Wen-Di Li, Haixiong Ge, Yong Hu
Nanoparticles for biomedical applications are generally formed by bottom-up approaches such as self-assembly, emulsification and precipitation. But these methods usually have critical limitations in fabrication of nanoparticles with controllable morphologies and monodispersed size. Compared with bottom-up methods, top-down nanofabrication techniques offer advantages of high fidelity and high controllability. This review focuses on top-down nanofabrication techniques for engineering particles along with their biomedical applications...
July 12, 2018: Advanced Drug Delivery Reviews
Janna C Nawroth, Riccardo Barrile, David Conegliano, Sander van Riet, Pieter S Hiemstra, Remi Villenave
Pathologies of the respiratory system such as lung infections, chronic inflammatory lung diseases, and lung cancer are among the leading causes of morbidity and mortality, killing one in six people worldwide. Development of more effective treatments is hindered by the lack of preclinical models of the human lung that can capture the disease complexity, highly heterogeneous disease phenotypes, and pharmacokinetics and pharmacodynamics observed in patients. The merger of two novel technologies, Organs-on-Chips and human stem cell engineering, has the potential to deliver such urgently needed models...
July 12, 2018: Advanced Drug Delivery Reviews
S Vijayavenkataraman, Wei-Cheng Yan, W F Lu, Chi-Hwa Wang, J Y H Fuh
3D bioprinting is a pioneering technology that enables fabrication of biomimetic, multiscale, multi-cellular tissues with highly complex tissue microenvironment, intricate cytoarchitecture, structure-function hierarchy, and tissue-specific compositional and mechanical heterogeneity. Given the huge demand for organ transplantation, coupled with limited organ donors, bioprinting is a potential technology that could solve this crisis of organ shortage by fabrication of fully-functional whole organs. Though organ bioprinting is a far-fetched goal, there has been a considerable and commendable progress in the field of bioprinting that could be used as transplantable tissues in regenerative medicine...
July 7, 2018: Advanced Drug Delivery Reviews
Pan Tao, Jingen Zhu, Marthandan Mahalingam, Himanshu Batra, Venigalla B Rao
Subunit vaccines containing one or more target antigens from pathogenic organisms represent safer alternatives to whole pathogen vaccines. However, the antigens by themselves are not sufficiently immunogenic and require additives known as adjuvants to enhance immunogenicity and protective efficacy. Assembly of the antigens into virus-like nanoparticles (VLPs) is a better approach as it allows presentation of the epitopes in a more native context. The repetitive, symmetrical, and high density display of antigens on the VLPs mimic pathogen-associated molecular patterns seen on bacteria and viruses...
July 5, 2018: Advanced Drug Delivery Reviews
Patricia Rousselle, Fabienne Braye, Guila Dayan
Cutaneous wound healing in adult mammals is a complex multi-step process involving overlapping stages of blood clot formation, inflammation, re-epithelialization, granulation tissue formation, neovascularization, and remodelling. Re-epithelialization describes the resurfacing of a wound with new epithelium. The cellular and molecular processes involved in the initiation, maintenance, and completion of epithelialization are essential for successful wound closure. A variety of modulators are involved, including growth factors, cytokines, matrix metalloproteinases, cellular receptors, and extracellular matrix components...
July 5, 2018: Advanced Drug Delivery Reviews
Sorah Yoon, John J Rossi
The structural flexibility and small size of aptamers enable precise recognition of cellular elements for imaging and therapeutic applications. The process by which aptamers are taken into cells depends on their targets but is typically clathrin-mediated endocytosis or macropinocytosis. After internalization, most aptamers are transported to endosomes, lysosomes, endoplasmic reticulum, Golgi apparatus, and occasionally mitochondria and autophagosomes. Intracellular aptamers, or "intramers," have versatile functions ranging from intracellular RNA imaging, gene regulation, and therapeutics to allosteric modulation, which we discuss in this review...
July 5, 2018: Advanced Drug Delivery Reviews
Arshad Mahmood, Andreas Bernkop-Schnürch
Since the development of self-emulsifying drug delivery systems (SEDDS) in 1980's, they attract the attention of researchers in order to confront the challenge of poor water-solubility of orally given drugs. Within recent years, SEDDS were also discovered for oral administration of hydrophilic macromolecular drugs such as peptides, proteins, polysaccharides and pDNA. Due to hydrophobic ion pairing (HIP) with oppositely charged lipophilic auxiliary agents the resulting complexes can be incorporated in the lipophilic phase of SEDDS...
July 4, 2018: Advanced Drug Delivery Reviews
Stefan Mühlebach
Nanomedicines and follow-on versions (in the EU also called nanosimilars) are on the market partially since decades although not recognizing their nano properties in the beginning; a substantial number is in clinical development. Nanomedicines are typically synthetic and belong to the non-biological complex drugs. They show a high variability in form, structure, and size. Also large molecule biologics show nano-characteristics meaning nano-dimension in size (1-100 nm) or specific properties related to these dimensions...
June 29, 2018: Advanced Drug Delivery Reviews
Niranjan G Kotla, Shubhasmin Rana, Gandhi Sivaraman, Omprakash Sunnapu, Praveen K Vemula, Abhay Pandit, Yury Rochev
Oral colon-specific delivery systems emerged as the main therapeutic cargos by making a significant impact in the field of modern medicine for local drug delivery in intestinal inflammation. The site-specific delivery of therapeutics (aminosalicylates, glucocorticoids, biologics) to the ulcerative mucus tissue can provide prominent advantages in mucosal healing (MH). Attaining gut mucosal healing and anti-fibrosis are main treatment outcomes in inflammatory bowel disease (IBD). The pharmaceutical strategies that are commonly used to achieve a colon-specific drug delivery system include time, pH-dependent polymer coating, prodrug, colonic microbiota-activated delivery systems and a combination of these approaches...
June 29, 2018: Advanced Drug Delivery Reviews
Can Zhang, Bei Xie, Yujian Zou, Dan Zhu, Lei Lei, Dapeng Zhao, Hemin Nie
The interaction of biological cells with artificial biomaterials is one of the most important issues in tissue engineering and regenerative medicine. The interaction is strongly governed by physical and chemical properties of the materials and displayed with differentiated cellular behaviors, including cell self-renewal, differentiation, reprogramming, dedifferentiation, or transdifferentiation as a result. A number of engineered biomaterials and micro- or nano-structures have been developed to mimic structural components of cell niche and specific function of extra cellular matrix (ECM) over past two decades...
June 29, 2018: Advanced Drug Delivery Reviews
Heather H Gustafson, Audrey Olshefsky, Meilyn Sylvestre, Drew L Sellers, Suzie H Pun
Targeting ligands are used in drug delivery to improve drug distribution to desired cells or tissues and to facilitate cellular entry. In vivo biopanning, whereby billions of potential ligand sequences are screened in biologically-relevant and complex conditions, is a powerful method for identification of novel target ligands. This tool has impacted drug delivery technologies and expanded our arsenal of therapeutics and diagnostics. Within this review we will discuss current in vivo panning technologies and ways that these technologies can be improved to advance next-generation drug delivery strategies...
June 28, 2018: Advanced Drug Delivery Reviews
James P K Armstrong, Molly M Stevens
Extracellular vesicles (EVs), nanoscale vectors used in intercellular communication, have demonstrated great promise as natural drug delivery systems. Recent reports have detailed impressive in vivo results from the administration of EVs pre-loaded with therapeutic cargo, including small molecules, nanoparticles, proteins and oligonucleotides. These results have sparked intensive research interest across a huge range of disease models. There are, however, enduring limitations that have restricted widespread clinical and pharmaceutical adoption...
June 27, 2018: Advanced Drug Delivery Reviews
Marco Siccardi, Steve Rannard, Andrew Owen
The use of solid drug nanoparticles (SDN) has become an established approach to improve drug delivery, supporting enhancement of oral absorption and long-acting administration strategies. A broad range of SDNs have been successfully utilised for multiple products and several development programmes are currently underway across different therapeutic areas. With some approaches, a large range of material space is available with diversity in physical characteristics, excipient choice and pharmacological behaviour...
June 27, 2018: Advanced Drug Delivery Reviews
Huan Meng, Andre E Nel
While chemotherapy is the only approved non-surgical option for the majority of pancreatic cancer patients, it rarely results in a cure. The failure to respond to chemotherapy is due to the presence of an abundant dysplastic stroma that interferes in drug delivery and as a result of drug resistance. It is appropriate, therefore, to consider the stromal contribution to the resistance to chemotherapy and sidestepping this barrier with nanocarriers that improve survival outcome. In this paper, we provide a short overview of the role of the stroma in chemotherapy resistance, including the use of nanocarriers to negate this barrier...
June 26, 2018: Advanced Drug Delivery Reviews
Amy Cochrane, Hugo J Albers, Robert Passier, Christine L Mummery, Albert van den Berg, Valeria V Orlova, Andries D van der Meer
The vascular system is one of the first to develop during embryogenesis and is essential for all organs and tissues in our body to develop and function. It has many essential roles including controlling the absorption, distribution and excretion of compounds and therefore determines the pharmacokinetics of drugs and therapeutics. Vascular homeostasis is under tight physiological control which is essential for maintaining tissues in a healthy state. Consequently, disruption of vascular homeostasis plays an integral role in many disease processes, making cells of the vessel wall attractive targets for therapeutic intervention...
June 23, 2018: Advanced Drug Delivery Reviews
Xuanyi Ma, Justin Liu, Wei Zhu, Min Tang, Natalie Lawrence, Claire Yu, Maling Gou, Shaochen Chen
3D bioprinting is emerging as a promising technology for fabricating complex tissue constructs with tailored biological components and mechanical properties. Recent advances have enabled scientists to precisely position materials and cells to build functional tissue models for in vitro drug screening and disease modeling. This review presents state-of-the-art 3D bioprinting techniques and discusses the choice of cell source and biomaterials for building functional tissue models that can be used for personalized drug screening and disease modeling...
June 21, 2018: Advanced Drug Delivery Reviews
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