A novel trans-lymphatic drug delivery system: Implantable gelatin sponge impregnated with PLGA-paclitaxel microspheres

A novel trans-lymphatic drug delivery system: Implantable gelatin sponge impregnated with PLGA-paclitaxel microspheres
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DOI:
10.1016/j.biomaterials.2007.03.022
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发表时间:
2007-07-01
期刊:
影响因子:
14
通讯作者:
Johnston, Michael R.
Johnston, Michael R.
中科院分区:
工程技术1区
文献类型:
--
作者:
Liu, Jiang;Meisner, Dale;Johnston, Michael R.

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描述了一种将聚丙交酯-共-乙交酯-紫杉醇(PLGA-PTX)或PLGA-罗丹明微球掺入明胶海绵基质中的经淋巴给药系统。该系统结合了PLGA-PTX的持续释放特性和明胶基质的结构优势,可以直接植入淋巴部位用于治疗和预防目的。采用喷雾干燥法制备PLGA微球。颗粒的尺寸范围为1-8 μ m,适合于腹膜内和胸膜内淋巴靶向递送。扫描电子显微镜显示PLGA微球在多孔海绵网络中均匀分布。PTX的释放主要受PLGA降解的控制。使用碳二亚胺交联明胶减少了海绵的生物降解,从而延迟了PLGA在体外的释放。在健康大鼠和携带原位肺癌的大鼠中评估体内淋巴递送。腹腔内和胸膜内植入的海绵浸渍与PLGA微球导致自发吸收的颗粒在淋巴系统。它的结论是,该系统提供了巨大的潜力,有针对性地提供治疗剂的淋巴系统,特别是在癌症的淋巴转移的控制。(C)2007爱思唯尔有限公司保留所有权利。
A translymphatic drug delivery system which incorporates poly-lactide-co-glycolide-paclitaxel (PLGA-PTX) or PLGA-rhodamine microspheres into gelatin sponge matrix is described. The system combines the sustained release properties of PLGA-PTX with the structural advantages of gelatin matrix that can be implanted directly to the lymphatic site for both therapeutic and prophylactic purposes. The PLGA microspheres were prepared using spray drying technique. The particles were in the size range of 1-8 mu m, suitable for intraperitoneal and intrapleural lymphatic targeting delivery. Scanning electron microscopy revealed the homogeneous distribution of PLGA microspheres in the porous sponge network. The release of PTX was mainly controlled by the degradation of the PLGA. Crosslinking gelatin using carbodiimide reduced the biodegradation of the sponge and thereby delayed the release of the PLGA in vitro. In vivo lymphatic delivery was assessed in both healthy rats and rats bearing orthotopic lung cancer. Intraperitoneal and intrapleural implantation of the sponge impregnated with PLGA microspheres resulted in spontaneous absorption of the particles in the lymphatic system. It is concluded that the system provides great potential for targeted delivery of therapeutic agent to the lymphatic system especially for the control of lymphatic metastasis in cancer. (C) 2007 Elsevier Ltd. All rights reserved.