Ci Tianyuan, Chen Liang, Yu Lin, Ding Jiandong
State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Advanced Materials Laboratory, Fudan University, Shanghai 200433, China.
1] State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Advanced Materials Laboratory, Fudan University, Shanghai 200433, China [2] Key Laboratory of Smart Drug Delivery of Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, China.
Sci Rep. 2014 Jul 1;4:5473. doi: 10.1038/srep05473.
For cancer chemotherapy, a tumor regression without any surgical resection and severe side effects is greatly preferred to merely slowing down the growth of tumors. Here, we report a formulation composed of irinotecan (IRN) and poly(D,L-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA). IRN is a clinically used antitumor drug with active and inactive chemical forms in equilibrium, and the major form at physiological conditions is inactive but still has side effects. The aqueous solution of the PLGA-PEG-PLGA is a sol at room temperature and physically gels at body temperature, forming a thermogel. We successfully mixed this moderately soluble drug into the amphiphilic copolymer aqueous solution for the first time. The mixture was subcutaneously injected into nude mice with xenografted SW620 human colon tumors. Excellent in vivo antitumor efficacy was observed in the group that received the IRN-loaded thermogel. The tumor was significantly regressed after being treated with the IRN/thermogel, and the side effects (blood toxicity and body weight decrease) were very mild. These results might be attributed to the ideal sustained release profile and period of release of the drug from the thermogel and to the significant enhancement of the fraction of the active form of the drug by the thermogel.
对于癌症化疗而言，相比于仅仅减缓肿瘤生长，在不进行任何手术切除且无严重副作用的情况下实现肿瘤消退是更为理想的。在此，我们报道了一种由伊立替康（IRN）和聚（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）组成的制剂。IRN是一种临床使用的抗肿瘤药物，其活性和非活性化学形式处于平衡状态，在生理条件下主要形式是非活性的，但仍有副作用。PLGA-PEG-PLGA的水溶液在室温下是溶胶，在体温下物理凝胶化，形成热凝胶。我们首次成功地将这种中度可溶性药物混入两亲共聚物水溶液中。将该混合物皮下注射到接种了SW620人结肠肿瘤的裸鼠体内。在接受负载IRN的热凝胶的组中观察到了优异的体内抗肿瘤效果。用IRN/热凝胶治疗后肿瘤明显消退，且副作用（血液毒性和体重减轻）非常轻微。这些结果可能归因于药物从热凝胶中的理想缓释曲线和释放期，以及热凝胶对药物活性形式比例的显著提高。
