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Abstract The recent decade has witnessed a growing demand to substitute synthetic materials with naturally-derived platforms for minimizing their undesirable footprints in biomedicine, environment, and ecosystems. Among the natural materials, cellulose, the most abundant biopolymer in the world with key properties, such as biocompatibility, biorenewability, and sustainability has drawn significant attention. The hierarchical structure of cellulose fibers, one of the main constituents of plant cell walls, has been nanoengineered and broken down to nanoscale building blocks, providing an infrastructure for nanomedicine. Microorganisms, such as certain types of bacteria, are another source of nanocelluloses known as bacterial nanocellulose (BNC), which benefit from high purity and crystallinity. Chemical and mechanical treatments of cellulose fibrils made up of alternating crystalline and amorphous regions have yielded cellulose nanocrystals (CNC), hairy CNC (HCNC), and cellulose nanofibrils (CNF) with dimensions spanning from a few nanometers up to several microns. Cellulose nanocrystals and nanofibrils may readily bind drugs, proteins, and nanoparticles through physical interactions or be chemically modified to covalently accommodate cargos. Engineering surface properties, such as chemical functionality, charge, area, crystallinity, and hydrophilicity, plays a pivotal role in controlling the cargo loading/releasing capacity and rate, stability, toxicity, immunogenicity, and biodegradation of nanocellulose-based delivery platforms. This review provides insights into the recent advances in nanoengineering cellulose crystals and fibrils to develop vehicles, encompassing colloidal nanoparticles, hydrogels, aerogels, films, coatings, capsules, and membranes, for the delivery of a broad range of bioactive cargos, such as chemotherapeutic drugs, anti-inflammatory agents, antibacterial compounds, and probiotics. Synopsis Engineering certain types of microorganisms as well as the hierarchical structure of cellulose fibers, one of the main building blocks of plant cell walls, has yielded unique families of cellulose-based nanomaterials, which have leveraged the effective delivery of bioactive molecules. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Novel microfluidic tools allow new ways to manufacture and test drug delivery systems. Organ-on-a-chip systems — microscale recapitulations of complex organ functions — promise to improve the drug development pipeline. This review highlights the importance of integrating microfluidic networks with 3D tissue engineered models to create organ-on-a-chip platforms, able to meet the demand of creating robust preclinical screening models. Specific examples are cited to demonstrate the use of these systems for studying the performance of drug delivery vectors and thereby reduce the discrepancies between their performance at preclinical and clinical trials. We also highlight the future directions that need to be pursued by the research community for these proof-of-concept studies to achieve the goal of accelerating clinical translation of drug delivery nanoparticles. [ABSTRACT FROM AUTHOR]

Abstract: The rapid advancement of nanotechnology has raised the possibility of using engineered nanoparticles that interact within biological environments for treatment of diseases. Nanoparticles interacting with cells and the extracellular environment can trigger a sequence of biological effects. These effects largely depend on the dynamic physicochemical characteristics of nanoparticles, which determine the biocompatibility and efficacy of the intended outcomes. Understanding the mechanisms behind these different outcomes will allow prediction of the relationship between nanostructures and their interactions with the biological milieu. At present, almost no standard biocompatibility evaluation criteria have been established, in particular for nanoparticles used in drug delivery systems. Therefore, an appropriate safety guideline of nanoparticles on human health with assessable endpoints is needed. In this review, we discuss the data existing in the literature regarding biocompatibility of nanoparticles for drug delivery applications. We also review the various types of nanoparticles used in drug delivery systems while addressing new challenges and research directions. Presenting the aforementioned information will aid in getting one step closer to formulating compatibility criteria for biological systems under exposure to different nanoparticles. [Copyright &y& Elsevier]