pH-Responsive Artesunate Polymer Prodrugs with Enhanced Ablation Effect on Rodent Xenograft Colon Cancer
| Autor: | Yan-Jun Chen, Feng Sui, Mi-Yi Yang, Hong Yi, Li Liu, Chen Zang, Qing-He Zhao, Dan-Li Hao, Ran Xie, Wei-Yan Cai, Gejing De, Hai Ma |
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| Rok vydání: | 2020 |
| Předmět: |
Drug
media_common.quotation_subject Biophysics Pharmaceutical Science Bioengineering 02 engineering and technology Pharmacology Conjugated system 010402 general chemistry 01 natural sciences Micelle Biomaterials chemistry.chemical_compound Drug Discovery media_common Chemistry Organic Chemistry General Medicine Prodrug 021001 nanoscience & nanotechnology In vitro 0104 chemical sciences Lactic acid Artesunate Titration 0210 nano-technology |
| Zdroj: | International Journal of Nanomedicine. 15:1771-1786 |
| ISSN: | 1178-2013 |
| DOI: | 10.2147/ijn.s242032 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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