RESUMO
To study the influence of polymer purity on microsphere characteristics, bovine serum albumin (BSA) loaded biodegradable microspheres were prepared by spray drying using two samples of poly(lactide-co-glycolide), PLG, (50:50, mwt = 35 and 69 kDa). Polymer properties were varied by DL-lactide and glycolide addition or by ultrafiltration. While the effective drug loading was not affected by polymer purity, Tg was decreased with increasing monomer and oligomer content. The removal of these low molecular weight substances by ultrafiltration led to a narrower molecular weight distribution compared to the untreated PLG. Concerning the polymer with the higher molecular weight, microsphere morphology was also strongly affected by polymer composition. In contrast to the non-modified PLG, monomer addition yielded particles with a much smoother surface structure. Moreover, in vitro cytotoxicity of the microspheres prepared from the polymer pretreated by ultrafiltration was significantly reduced, whereas monomer addition caused a dramatic decrease of cells surviving contact with the microsphere extract. The in vivo degradation rate of the ultrafiltered microspheres was decreased and as a result, protein release at later times was slowed down. Furthermore, depending on the effective drug loading level, monomer addition resulted in a decrease in the initial protein burst. It can be concluded that the effect of low molecular weight impurities in a polymer on microsphere characteristics and on cytotoxicity cannot be ignored. Their elimination is possible by ultrafiltration.
Assuntos
Soroalbumina Bovina/química , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Materiais Biocompatíveis , Varredura Diferencial de Calorimetria , Sobrevivência Celular/efeitos dos fármacos , Fenômenos Químicos , Físico-Química , Cromatografia em Gel , Ácido Láctico , Camundongos , Microscopia Eletrônica de Varredura , Microesferas , Peso Molecular , Tamanho da Partícula , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros , UltrafiltraçãoRESUMO
Films of three ABA-block copolymers composed of lactic-co-glycolic acid A blocks and poly(oxyethylene) (PEO) B blocks and one random lactic-co-glycolic acid copolymer (PLG) were studied to investigate the influence of different polymer compositions and molecular weights on the tissue reaction, appearance of toxic degradation products, and swelling behavior in the cage implant system in rats. The inflammatory tissue reaction was followed over a 21-day implantation period by monitoring the leukocyte concentration, the extracellular acid, and alkaline phosphatase activities in a quantitative manner. Size and density of adherent macrophages and foreign body giant cells on the film surfaces were determined. The ABA and PLG implants caused only a minimal inflammatory reaction, as characterized by a low concentration of leukocytes during the implantation period when compared to empty cage controls. The content of PEO had an influence on the density of the adherent cells on the surface of the polymer film. An increase in PEO content and molecular weight decreased the cellular density during the implantation period. As demonstrated by scanning electron microscopy, no degradation was observed for all polymers during the implantation period. Our results demonstrate that the ABA block copolymers and PLG copolymer, are equally well tolerated in the cage implant test system.
