RESUMO
For the multi-reservoir type microspheres composed of poly(dl-lactide-co-glycolide) (PLGA) and poly(dl-lactide) (PLA), the influence of the drug-holding layer and the non-drug-holding layer on drug release profiles was studied. The microspheres with the blend of PLGA and PLA were prepared by the W/O type emulsion-solvent evaporation technique, and cisplatin was used as a model drug. The degree of water uptake and the erosion of each polymer were evaluated to clarify the mechanism of drug release for multi-reservoir type microspheres. The blending of PLA and PLGA provided two types of microspheres in terms of the drug distribution in a microsphere, depending on the ratio of the blend: the microspheres with the drug-holding layer covered by the non-drug layer and the microspheres with the drug on the outer region. The drug release in the early period was governed by the pattern of drug distribution. The drug release rate at a steady state was governed by the erosion of the drug-holding layer. The results of present study indicate that drug release from multi-reservoir type microspheres involves the following process: (a) rapid release of the drug near the surface of microspheres, (b) formation of micropores in the non-drug-holding layer by hydration and erosion, (c) degradation of the drug-holding layer, and (d) diffusion of the drug through micropores.
Assuntos
Antineoplásicos/química , Cisplatino/química , Ácido Láctico/química , Microesferas , Poliésteres/química , Ácido Poliglicólico/química , Polímeros/química , Portadores de Fármacos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Água/químicaRESUMO
Transport characteristics of intact albumin were investigated using primary cultured rat alveolar epithelial cell monolayers. The apical-to-basolateral (ab) flux of intact fluorescein isothiocyanate (FITC)-labeled albumin (F-Alb) is greater than basolateral-to-apical (ba) flux at the same upstream [F-Alb]. Net absorption of intact F-Alb occurs with half-maximal concentration of approximately 1.6 microM and maximal transport rate of approximately 0.15 fmol.cm(-2).s(-1). At 15 and 4 degrees C, both ab and ba F-Alb fluxes are not different from zero, collapsing net absorption. The presence of excess unlabeled albumin (but not other macromolecule species) in either the apical or basolateral fluid significantly reduces both ab and ba unidirectional F-Alb fluxes. Photoaffinity labeling of apical cell membranes revealed an approximately 60-kDa protein that exhibits specificity for albumin. These data indicate that net absorption of intact albumin takes place via saturable receptor-mediated transcellular endocytotic processes recognizing albumin, but not other macromolecules, that may play an important role in alveolar homeostasis in the mammalian lung.