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

被引:75
作者
Liu, Jiang
Meisner, Dale
Kwong, Elizabeth
Wu, Xiao Y.
Johnston, Michael R.
机构
[1] Univ Toronto, Fac Med, Inst Med Sci, Toronto, ON, Canada
[2] Univ Toronto, Fac Med, Dept Surg, Toronto, ON M5S 1A1, Canada
[3] Univ Toronto, Fac Pharm, Dept Pharmaceut Sci, Toronto, ON, Canada
[4] Merck Frosst Ctr Therapeut Res, Kirkland, PQ, Canada
基金
加拿大健康研究院; 加拿大自然科学与工程研究理事会;
关键词
lymphatic drug delivery; gelatin sponge; PLGA-paclitaxel microspheres; controlled release; cancer;
D O I
10.1016/j.biomaterials.2007.03.022
中图分类号
R318 [生物医学工程];
学科分类号
0831 [生物医学工程];
摘要
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.
引用
收藏
页码:3236 / 3244
页数:9
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