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pH-Responsive Artesunate Polymer Prodrugs with Enhanced Ablation Effect on Rodent Xenograft Colon Cancer

Authors Hao DL, Xie R, De GJ, Yi H, Zang C, Yang MY, Liu L, Ma H, Cai WY, Zhao QH, Sui F, Chen YJ

Received 12 December 2019

Accepted for publication 2 March 2020

Published 16 March 2020 Volume 2020:15 Pages 1771—1786

DOI https://doi.org/10.2147/IJN.S242032

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Yan Shen


Dan-Li Hao, Ran Xie, Ge-Jing De, Hong Yi, Chen Zang, Mi-Yi Yang, Li Liu, Hai Ma, Wei-Yan Cai, Qing-He Zhao, Feng Sui, Yan-Jun Chen

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, People’s Republic of China

Correspondence: Qing-He Zhao; Yan-Jun Chen Tel/ Fax +86-10-84036059
Email qhzhao@icmm.ac.cn; yjchen@icmm.ac.cn

Purpose: In this study, pH-sensitive poly(2-ethyl-2-oxazoline)-poly(lactic acid)-poly(β-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°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.

Keywords: artesunate, micelles, pH responsive, polymer prodrug, poly(2-ethyl-2-oxazoline), poly(β-amino ester)

Corrigendum for this paper has been published

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