Thermosensitive poly-(d,l-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly-(d,l-lactide-co-glycolide) hydrogels for multi-drug delivery.
Thermosensitive poly-(d,l-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly-(d,l-lactide-co-glycolide) hydrogels for multi-drug delivery.
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DOI：
10.3109/1061186x.2014.931406
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发表时间：
2014-08
影响因子：
4.5
通讯作者：
Kwon GS
中科院分区：
文献类型：
--
作者：
Cho H;Kwon GS
目前腹膜卵巢癌的治疗策略是腹膜手术和以多种药物为基础的化疗相结合，通常包括腹膜内注射(IP)。温度敏感的聚(D，L-丙交酯-co-乙交酯)-嵌段-聚乙二醇聚(D，L-丙交酯-co-乙交酯)(PLGA-b-PEGb-PLGA)水凝胶平台(热凝胶)使难于加工的紫杉醇(细胞毒剂)、17-烯丙氨基-17-去甲氧基格尔达霉素(17-AAG，热休克蛋白抑制剂)和雷帕霉素(雷帕霉素蛋白抑制剂的哺乳动物靶标)能够进行凝胶负载。携带紫杉醇、17-AAG和雷帕霉素(名为Triogel)的PLGA-b-PEG-b-PLGA热凝胶(15%)成功地从室温以下的自由流动溶液转变为体温下的凝胶库。作为对物理凝胶侵蚀的响应，Triogel以相同的释放速率逐渐释放紫杉醇、17-AAG和雷帕霉素。在ES-2-Luc卵巢癌移植瘤模型中，单次ip Triogel(紫杉醇、17-AAG和雷帕霉素分别为60、60和30 mg/kg)可显著减轻荷瘤裸鼠的肿瘤负担，延长荷瘤裸鼠的存活时间，且无明显的全身毒性，与聚乙二醇嵌段聚(D，L-乳酸)胶束溶液注射或静脉注射(IV)相比。这些结果表明，携带多种药物的可生物降解热凝胶平台在腹膜卵巢癌的IP化疗中具有很大的潜力。
A current treatment strategy for peritoneal ovarian cancer is a combination of peritoneal surgery and multi-drug-based chemotherapy that often involves intraperitoneal (IP) injection. A thermosensitive poly-(D,L-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly-(D,L-lactide-co-glycolide) (PLGA-b-PEG-b-PLGA) hydrogel platform (thermogels) enabled gel loading of poorly work-soluble paclitaxel (cytotoxic agent), 17-allylamino-17-demethoxygeldanamycin (17-AAG, heat shock protein inhibitor), and rapamycin (mammalian target of rapamycin protein inhibitor). PLGA-b-PEG-b-PLGA thermogels (15%) carrying paclitaxel, 17-AAG, and rapamycin (named Triogel) made a successful transition from a free-flowing solution below ambient temperature to a gel depot at body temperature. Triogel gradually released paclitaxel, 17-AAG, and rapamycin at an equal release rate in response to the physical gel erosion. In an ES-2-luc ovarian cancer xenograft model, a single IP injection of Triogel (60, 60, and 30 mg/kg of paclitaxel, 17-AAG, and rapamycin, respectively) significantly reduced tumor burden and prolonged survival of ES-2-luc-bearing nude mice without notable systemic toxicity relative to those delivered by poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-b-PLA) micelles in solution via IP or intravenous (IV) injection route. These results show a great potential of a biodegradable thermogel platform carrying multi-drugs for IP chemotherapy in peritoneal ovarian cancer.