DEVELOPMENT OF BIODEGRADABLE POLYMERIC PASTE FORMULATIONS FOR TAXOL -AN IN-VITRO AND IN-VIVO STUDY

Biodegradable polymeric paste formulations ('surgical pastes') for loc al delivery of taxol were developed and characterized. Taxol was mixed into melted poly(D,L-lactide)-block-poly(ethylene glycol)-block-poly( D,L-lactide) (PDLLA-PEG-PDLLA) copolymers and blends of low molecular weight poly(D,L-lactic acid) and poly-epsilon-caprolactone (PDLLA:PCL) to obtain the paste formulations. The release of taxol into PBS album in buffer was measured by HPLC. The polymers and pastes were character ized by gel permeation chromatography (GPC), differential scanning cal orimetry (DSC), nuclear magnetic resonance (NMR) and scanning electron microscopy (SEM). Taxol was released in a sustained manner from the P DLLA-PEG-PDLLA paste over a period of 2 months by diffusion and polyme r erosion. The release from the blend was mainly erosion controlled an d consisted of a burst followed by a period of slow release. Efficacy of the pastes in inhibiting tumor growth in mice was evaluated. Molten , taxol loaded paste formulations were placed at subcutaneous tumor si tes in mice (pastes harden at 37 degrees C). After 16 days, the reduct ion in tumor weight was measured. Both the taxol loaded copolymer and 90:10 PDLLA:PCL blend formulations significantly inhibited tumor growt h in mice. The pastes with faster in vitro release rates resulted in g reater efficacy in inhibiting tumor growth. The results showed that bi odegradable polymeric surgical pastes are promising formulations for t he local delivery of taxol to inhibit tumor growth.