期刊论文详细信息
Drug Delivery
Localized co-delivery of collagenase and trastuzumab by thermosensitive hydrogels for enhanced antitumor efficacy in human breast xenograft
Wenbing Dai1  Qiang Zhang1  Anni Pan1  Xueqing Wang1  Zhaoyang Wang1  Binlong Chen1  Yiguang Wang1  Bing He1  Hua Zhang1 
[1] State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University;
关键词: thermosensitive hydrogel;    trastuzumab;    collagenase;    sustained release;    antitumor efficacy;   
DOI  :  10.1080/10717544.2018.1474971
来源: DOAJ
【 摘 要 】

Modulation of the collagen-rich extracellular matrix (ECM) in solid tumors by the treatment with collagenase has been proved effective in enhancement of the interstitial transport and antitumor efficacy of antibodies. We, therefore, developed a PLGA-PEG-PLGA polymer-based thermosensitive hydrogel, which incorporated a HER2-targeted monoclonal antibody trastuzumab and collagenase (Col/Tra/Gel) for peritumoral administration. HER2-positvie BT474 tumor-bearing mice were selected as a model. The Col/Tra/Gel showed the continuous and biphasic release of protein drugs for 9 days in vitro. NIR imaging studies demonstrated a long-term retention of Col/Tra/Gel hydrogel in the peritumoral area for over 20 days. Treatment with Col/Tra/Gel reduced the collagen density and enhanced apoptotic cell death in tumor tissue, resulting in superior treatments with increased efficacy and reduced toxicity compared with other control groups. Moreover, a quarter-dose of Col/Tra/Gel exhibited a better antitumor efficacy than that of intravenous injection of clinical trastuzumab formulation. This localized co-delivery system offers a potential strategy for the modulation of dense ECM and enhancement of antibody efficacy.

【 授权许可】

Unknown   

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