A novel trans-lymphatic drug delivery system: implantable gelatin sponge impregnated with PLGA-paclitaxel microspheres.
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 microm, 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.
Liu
Jiang
J
Institute of Medical Science and Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, Ont., Canada. jiang.liu@utoronto.ca
Meisner
Dale
D
Kwong
Elizabeth
E
Wu
Xiao Y
XY
Johnston
Michael R
MR
D020341:Absorbable Implants; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D005780:Gelatin / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D042601:Lymphatic Vessels / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D008863:Microspheres; D008970:Molecular Weight; D017239:Paclitaxel / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D016062:Porosity; D011208:Powders; D051381:Rats; D011923:Rats, Nude; D017207:Rats, Sprague-Dawley
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D011108:Polymers; D011208:Powders; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005780:Gelatin; D017239:Paclitaxel