BIODEGRADABLE POLYESTERS FOR CONTROLLED-RELEASE OF TRYPANOCIDAL DRUGS- IN-VITRO AND IN-VIVO STUDIES

Copolymers of epsilon-caprolactone and L-lactide P(CL-LLA), epsilon-ca prolactone and D,L-lactide P(CL-DLLA) and epsilon-caprolactone and tri methylene carbonate P(CL-TMC) were synthesized. The composition of com onomers and their sequence lengths were determined by means of H-1 and C-13 NMR measurements. The effect of the comonomer on the thermal pro perties was investigated by differential scanning calorimetry (DSC) an alysis. The in vitro degradation of the rods obtained by melt extrusio n of the synthesized copolymers and the commercial homopolymers poly(e psilon-caprolactone) P(CL) and poly(D,L-lactide) P(DLLA) was carried o ut in phosphate buffer (PB) pH 7.4 at 37 degrees C. The rate of degrad ation depends on comonomers and polymer composition. The in vitro rele ase of the selected drugs, isometamidium chloride (IMM) and ethidium b romide (EtBr), from such devices was carried out under the same condit ions as used for the in vitro degradation. The release experiments sho w that the release of IMM is faster than for EtBr. During the first st age, for IMM the release is governed by osmotic pressure whereas for E tBr the release is mainly diffusion-controlled The in vitro release of these drugs is governed by polymer matrix degradation at the later st age of the release process. Comparative in vitro release study from th e different polymers showed that the release depends mainly on the phy sical properties of the polymer. The in vivo experiments carried out i n the held on cattle and in the laboratory on rabbits using the classi cal treatment (intramuscular injection) and the sustained release devi ces (SRD) subcutaneously implanted, showed that the prophylactic perio d is significantly enhanced in the case of SRD as compared to intramus cular injection. The comparative efficacy of SRD containing IMM and Et Br evaluated in the case of rabbits showed that, the SRD (IMM) prophyl actic period is much longer than for SRD (EtBr). (C) 1998 Published by Elsevier Science Ltd. All rights reserved.