NDLI: pH and reduction dual responsive cross-linked polyurethane micelles as an intracellular drug delivery system

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pH and reduction dual responsive cross-linked polyurethane micelles as an intracellular drug delivery system

Content Provider	Semantic Scholar
Author	Yu, Shuangjiang He, Chaoliang Lv, Qiang Chen, Xuesi
Copyright Year	2014
Abstract	Nano-vehicles that exhibit enhanced stability in blood circulation while spontaneously releasing therapeutic cargos at pathological sites in response to specific biological triggers are of interest for on-demand drug delivery. In this work, disulfide cross-linked polyurethane micelles (CL-PUMs) that respond to pH change and an intracellular reducing agent were developed. The micelles were prepared by cross-linking of poly(ethylene glycol)–polyurethane multiblock copolymers containing tertiary amino and cyclic disulfide moieties via a thiol–disulfide exchange reaction. The CL-PUMs tended to swell or decompose under a weakly acidic environment or in the presence of an intracellular reducing agent, glutathione (GSH), likely owing to the protonation of the tertiary amino groups and cleavage of the disulfide cross-linking bonds. The doxorubicin (DOX)-loaded CL-PUMs suppressed the initial burst release at pH 7.4 without GSH, while they displayed a triggered drug release manner in response to an acidic environment and GSH. It was found that the intracellular DOX release of the DOX-loaded CL-PUMs in HepG2 cells was accelerated by an acidic environment or enhanced intracellular GSH concentration. Moreover, the time-dependent cytotoxicity against HepG2 and HeLa cells of the DOX-loaded CL-PUMs was confirmed by an MTT assay. Overall, due to the enhanced stability, selective swelling and decomposition properties in response to intracellular micro-environments, the pH- and reduction-sensitive polyurethane cross-linked nano-carriers can serve as a potential system for intracellular drug delivery.
Starting Page	63070
Ending Page	63078
Page Count	9
File Format	PDF HTM / HTML
DOI	10.1039/C4RA14221G
Volume Number	4
Alternate Webpage(s)	http://pubs.rsc.org/en/content/getauthorversionpdf/C4RA14221G
Alternate Webpage(s)	https://doi.org/10.1039/C4RA14221G
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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