Doxorubicin-induced co-assembling nanomedicines with temperature-sensitive acidic polymer and their in-situ-forming hydrogels for intratumoral administration

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• 作者：Jiangshan Wan ; Shinan Geng ; Hao Zhao ; Xiaole Peng ; Qing Zhou ; Han Li ; Ming He ; Yanbing Zhao ; ^{zhaoyb@hust.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Xiangliang Yang ; ^{yangxl@hust.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Huibi Xu
• 关键词：Co-assembling ; Temperature sensitive ; Nanomedicines ; In-situ-forming hydrogels ; Intratumoral injection)
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：10 August 2016
• 年：2016
• 卷：235
• 期：Complete
• 页码：328-336
• 全文大小：1499 K

文摘

Doxorubicin (DOX)-induced co-assembling nanomedicines (D-PNAx) with temperature-sensitive PNAx triblock polymers have been developed for regional chemotherapy against liver cancer via intratumoral administration in the present work. Owing to the formation of insoluble DOX carboxylate, D-PNAx nanomedicines showed high drug-loading and entrapment efficacy via a simple mixing of doxorubicin hydrochloride and PNAx polymers. The sustained releasing profile of D-PNA100 nanomedicines indicated that only 9.4% of DOX was released within 1 day, and 60% was released during 10 days. Based on DOX-induced co-assembling behavior and their temperature sensitive in-situ-forming hydrogels, D-PNA100 nanomedicines showed excellent antitumor activity against H22 tumor using intratumoral administration. In contrast to that by free DOX solution (1.13 ± 0.04 times at 9 days) and blank PNA100 (2.11 ± 0.34 times), the tumor volume treated by D-PNA100 had been falling to only 0.77 ± 0.13 times of original tumor volume throughout the experimental period. In vivo biodistribution of DOX indicated that D-PNA100 nanomedicines exhibited much stronger DOX retention in tumor tissues than free DOX solution via intratumoral injection. D-PNA100 nanomedicines were hopeful to be developed as new temperature sensitive in-situ-forming hydrogels via i.t. injection for regional chemotherapy.