期刊
INTERNATIONAL JOURNAL OF NANOMEDICINE
卷 15, 期 -, 页码 1771-1786出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S242032
关键词
artesunate; micelles; pH responsive; polymer prodrug; poly(2-ethyl-2-oxazoline); poly(beta-amino ester)
资金
- Natural Science Foundation of China [81974461]
- National S&T Major Project of China [2018ZX09201011]
- Natural Science Foundation of Beijing Municipality [2192060]
Purpose: In this study, pH-sensitive poly(2-ethyl-2-oxazoline)-poly(lactic acid)-poly(beta-amino ester) (PEOz-PLA-PBAE) triblock copolymers were synthesized and were conjugated with an antimalaria drug artesunate (ART), for inhibition of a colon cancer xenograft model. Methods: The as-prepared polymer prodrugs are tended to self-assemble into polymeric micelles in aqueous milieu, with PEOz segment as hydrophilic shell and PLA-PBAE segment as hydrophobic core. Results: The pH sensitivity of the as-prepared copolymers was confirmed by acid-base titration with pKb values around 6.5. The drug-conjugated polymer micelles showed high stability for at least 96 h in PBS and 37 degrees C, respectively. The as-prepared copolymer prodrugs showed high drug loading content, with 9.57%+/- 1.24% of drug loading for PEOz-PLA-PBAE-ART4. The conjugated ART could be released in a sustained and pH-dependent manner, with 92% of released drug at pH 6.0 and 57% of drug released at pH 7.4, respectively. In addition, in vitro experiments showed higher inhibitory effect of the prodrugs on rodent CT-26 cells than that of free ART. Animal studies also demonstrated the enhanced inhibitory efficacy of PEOz-PLA-PBAE-ART2 micelles on the growth of rodent xenograft tumor. Conclusion: The pH-responsive artesunate polymer prodrugs are promising candidates for colon cancer adjuvant therapy.
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