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The physicochemical properties of NCs like size, shape, biodegradability, drug release characteristics, and surface chemistry have been shown to affect their performance in vivo. Well-designed NCs are able to release the encapsulated payload in a controlled manner or to change their structure in response to a variety of stimuli such as temperature, pH, enzymes, or reducing environments. NCs can be assembled from a variety of synthetic or naturally-derived excipients, including surfactants such as phospholipids, polymeric excipients such as poly(lactic- co-glycolic acid) (PLGA), inorganic materials like mesoporous silica and amphiphilic peptides. As the potential of such delivery systems is continuously proven in clinical trials, the number of nanomedicines available to patients is increasing and their efficacy is further improved, NCs are an ever-expanding area. As such, NCs can overcome critical issues such as a rapid clearance, unintended distribution, and poor bioavailability. Furthermore, NCs can be designed to promote drug transport across the cell membrane and to deliver drugs in a controlled and targeted manner. NCs have been shown to improve the solubility of encapsulated drugs and to prevent them from interacting with the biological environment on the way to their target, which may lead to premature degradation. This review focuses on the surface chemistry of NCs providing the best compromise between bioinert and stealth versus interactive features.Īdvances in nanomedicine have generated a broad range of engineered nanocarriers (NCs) for drug delivery applications. A deepened understanding of how these different approaches influence the performance of NCs in the body is of particular importance in order to improve their efficacy. Stimuli-responsive surfaces able to convert from bioinert and stealth to interactive at the target site have been recently introduced.
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Alternatively, surface structures interacting preferentially with the membrane of target cells can be utilized. These key surface properties-bioinert and stealth versus interactive at the target site-are in contradiction to each other so that the best compromise between them has to be found.
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Bioinert and stealth surface features are advantageous to avoid unintended interactions with endogenous surfaces at off-target sites and with the immune system, whereas at the target site these carriers should be highly interactive guaranteeing intracellular delivery of their payload. Their performance strongly depends on the surface chemistry, which governs their interaction with the biological environment. Nanocarriers (NCs) have emerged as powerful tools to improve drug solubility, to promote drug transport across membranes, to protect their payload from premature degradation, and to deliver drugs in a controlled and targeted manner.