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 PLGAÒpaclitaxel microspheres
Received 6 January 2007; accepted 15 March 2007. Available online 24 March 2007
Jiang Liua, , , Dale Meisnerb, Elizabeth Kwongb, Xiao Y. Wuc and Michael R. Johnstona
Biomaterials
Volume 28, Issue 21, July 2007,
ScienceDirect
Copyright © 2007 Elsevier Ltd All rights reserved.
aInstitute of Medical Science and Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, Ont., Canada
bPharmaceutical Research and Development, Merck Frosst Center for Therapeutic Research, 16711 Trans-Canada Highway, Kirkland, Que., Canada
cDepartment of Pharmaceutical Science, Faculty of Pharmacy, University of Toronto, Toronto, Ont., Canada
Abstract
A translymphatic drug delivery system which incorporates poly-lactide-co-glycolideÒpaclitaxel (PLGAÒPTX) or PLGAÒrhodamine microspheres into gelatin sponge matrix is described. The system combines the sustained release properties of PLGAÒPTX 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 1Ò8 µm, 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.
Keywords: Lymphatic drug delivery; Gelatin sponge; PLGA-paclitaxel microspheres; Controlled release; Cancer
Corresponding author. Princess Margaret Hospital/Ontario Cancer Institute, 610 University Avenue, Suite 7-611, Toronto, Ont., Canada M5G 2M9. Tel.: +1 416 946 2000x5617; fax: +1 416 340 3660.
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