Nagahama Koji, Kawano Daichi, Oyama Naho, Takemoto Ayaka, Kumano Takayuki, Kawakami Junji
Department of Nanobiochemistry, Frontiers of Innovative Research in Science and Technology, Konan University , 7-1-20 minatojima-minamimachi, Kobe 650-0047, Japan.
Biomacromolecules. 2015 Mar 9;16(3):880-9. doi: 10.1021/bm5017805. Epub 2015 Feb 10.
The purpose of this study was to fabricate a safe and effective doxorubicin (DOX)-delivery system for focal cancer chemotherapy. A novel biodegradable injectable gel was developed through self-assembly of poly(D,L-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) copolymer micelles, clay nanodisks (CNDs), and DOX. We discovered that DOX loaded in the hybrid gels acts as an anticancer drug and as a building block to organize new gel networks. Accordingly, long-term sustained release of DOX from hybrid injectable gels without initial burst release was achieved. Moreover, it was revealed that the DOX incorporated into gel networks controls its own release profile. This hybrid injectable gel is a self-controlled drug release system, which is a novel concept in controlled drug release. Importantly, a single injection of PLGA-PEG-PLGA/CND/DOX hybrid gel provides long-term sustained antitumor activity in vivo against human xenograft tumors in mice, suggesting the potential of hybrid gels as a valuable local DOX-delivery platform for cancer focal therapy.
本研究的目的是制备一种用于局部癌症化疗的安全有效的阿霉素（DOX）递送系统。通过聚（D，L-丙交酯-共-乙交酯）-b-聚（乙二醇）-b-聚（D，L-丙交酯-共-乙交酯）（PLGA-PEG-PLGA）共聚物胶束、粘土纳米盘（CNDs）和DOX的自组装，开发了一种新型的可生物降解注射凝胶。我们发现，负载在混合凝胶中的DOX既作为抗癌药物，又作为构建新凝胶网络的结构单元。因此，实现了DOX从混合注射凝胶中的长期持续释放，且无初始突释。此外，还发现掺入凝胶网络中的DOX控制其自身的释放曲线。这种混合注射凝胶是一种自控制药物释放系统，这在控释领域是一个新概念。重要的是，单次注射PLGA-PEG-PLGA/CND/DOX混合凝胶在体内对小鼠人异种移植肿瘤具有长期持续的抗肿瘤活性，表明混合凝胶作为一种有价值的局部DOX递送平台用于癌症局部治疗的潜力。
