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Redox and pH dual sensitive folate-modified star-like amphiphilic copolymer based on castor oil for controlled doxorubicin delivery

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Abstract To overcome the problems associated with the use of doxorubicin (DOX), such as low solubility, high toxicity, and side effects, a redox and pH-sensitive drug delivery system based on… Click to show full abstract

Abstract To overcome the problems associated with the use of doxorubicin (DOX), such as low solubility, high toxicity, and side effects, a redox and pH-sensitive drug delivery system based on a star-like copolymer of folate-modified poly (ethylene glycol) (PEG) and biodegradable castor oil was developed. Redox-sensitive disulfide linkage and pH-sensitive imine linkage were incorporated in the backbone of the star-like copolymer, which self-assembled into stable micelles with small particle size (91.67 nm), narrow size distribution, and low CMC value (2.7 mg/L). The disassembly behaviors of the micelles when exposed to endolysosomal pH of 5.5 and a high concentration of GSH were evaluated by scanning electron microscope from the changes of micellar morphology. The micelles were used to load DOX into the hydrophobic core. Drug loading capacity (DLC) and drug loading efficiency (DLE) were calculated to be 15.93% and 96.13%, respectively. In vitro release studies showed that DOX release from micelles followed a redox and pH-triggered manner. The introduction of dual trigger further expedited DOX release. In vitro cytotoxicity of the copolymer against HDF cells was investigated. The star-like copolymer showed no toxicity. While the DOX-loaded micelles suggested enhanced cytotoxicity against HeLa cells. These results indicated that these redox and pH-sensitive micelles have the potential as a nanocarrier for DOX and other hydrophobic anti-cancer drugs.

Keywords: star like; folate modified; copolymer; delivery; castor oil

Journal Title: Journal of Drug Delivery Science and Technology
Year Published: 2021

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