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.

Translymphatic chemotherapy by intrapleural placement of gelatin sponge containing biodegradable Paclitaxel colloids controls lymphatic metastasis in lung cancer.

As a means of treating lymphatic metastasis from lung cancer, the pharmacokinetics and therapeutic effects of an intrapleural (ipl) implantable drug delivery system consisting of a gelatin sponge impregnated with polylactide-co-glycolide paclitaxel (PLGA-PTX) microspheres were studied. PLGA-PTX with 7% (w/w) drug loading were incorporated into gelatin matrix. The pharmacokinetics were studied in rats with one of the following regimens: (a) Taxol 8 mg/kg by i.v. injection; (b) Taxol 8 mg/kg ipl; (c) PLGA-PTX (100 mg/kg) ipl; (d) sponge containing PLGA-PTX (100 mg/kg) ipl. PTX concentrations in lymph node and plasma were determined by liquid chromatography mass spectrometry, and the area under the curve (AUC) was calculated. Therapeutic efficacy was assessed in an orthotopic lung cancer model with tumor resection 14 days following tumor implantation. Animals were randomized to ipl placement of PLGA-PTX sponge, placebo sponge, or no treatment. Lymph node metastases were examined at 32 d. The results show that the mediastinal lymph node AUC was significantly higher with ipl. placement of PLGA-PTX sponge compared with i.v. and ipl administration of Taxol. This represents 100- to 400-fold increase of lymphatic drug exposure compared with i.v. dosing. Peak plasma concentration was significantly reduced in the PLGA-PTX sponge group compared with i.v. dosing. PLGA-PTX particles were microscopically identified in lymphatic tissue and resulted in an 80% reduction of lymphatic metastasis compared with controls. Translymphatic-targeted drug delivery significantly decreases lymphatic metastasis in an orthotopic lung cancer model. This effect may be attributable to the improved distribution of PTX to the lymphatic system.