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KMID : 1146920220520040427
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Journal of Pharmaceutical Investigation
2022 Volume.52 No. 4 p.427 ~ p.441
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Smart pH-responsive nanomedicines for disease therapy
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Shinn Jong-Yoon
Kwon Nu-Ri
Lee Seon-Ah
Lee Yong-Hyun
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Abstract
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Background: Currently nanomedicines are the focus of attention from researchers and clinicians because of the successes of lipid-nanoparticles-based COVID-19 vaccines. Nanoparticles improve existing treatments by providing a number of advantages including protection of cargo molecules from external stresses, delivery of drugs to target tissues, and sustained drug release. To prevent premature release-related side effects, stable drug loading in nanoformulations is required, but the increased stability of the formulation could also lead to a poor drug-release profile at the target sites. Thus, researchers have exploited differences in a range of properties (e.g., enzyme levels, pH, levels of reduced glutathione, and reactive oxygen species) between non-target and target sites for site-specific release of drugs. Among these environmental stimuli, pH gradients have been widely used to design novel, responsive nanoparticles.
Area covered: In this review, we assess drug delivery based on pH-responsive nanoparticles at the levels of tissues (tumor microenvironment, pH?~?6.5) and of intracellular compartments (endosome and lysosome, pH 4.5?6.5). Upon exposure to these pH stimuli, pH-responsive nanoparticles respond with physicochemical changes to their material structure and surface characteristics. These changes include swelling, dissociation, or surface charge switching, in a manner that favors drug release at the target site (the tumor microenvironment region and the cytosol followed by endosomal escape) rather than the surrounding tissues.
Expert opinion: Lastly, we consider the challenges involved in the development of pH-responsive nanomedicines.
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KEYWORD
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Nanomedicines, pH-responsiveness, Tumor microenvironment, Endosomal escape
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