Development and characterization of double walled microspheres from poly(L-lactide) and poly(D,L-lactide-co-glycolide) blends.

摘要

Double walled microspheres were developed from biodegradable polymers, poly(l-lactide), PLLA and poly(d,l-lactide-co-glycolide), PLGA, by the solvent evaporation microencapsulation process. PLLA and PLGA are the polymers of choice in drug delivery due to their versatility in terms of degradation that can be varied depending on their molecular weight and monomer ratios. The binary blend of PLLA and PLGA in methylene chloride phase separates to form double walled microspheres with an outer layer rich in PLLA and the inner core predominantly rich in PLGA. The PLLA PLGA phase separation behavior has been well characterized using a ternary phase diagram and the orientation of the phases within an aqueous environment has been illustrated using Harkin's equations for emulsion theory. Two model agents, fluorescent labeled bovine serum albumin, FITC-BSA, representing a hydrophilic agent and iron oxide representing a hydrophobic agent, were localized in either one of the two layers. Manipulating the relative polymer ratio at constant overall polymer concentration and the polymer in which the agent is introduced during the pre-encapsulation steps allowed for control of the localization. Double walled microspheres with the protein localized in the inner core had several advantages in that it reduced burst effects associated with protein encapsulated near the surface of the microspheres where the outer layer acted as a modulator and controlled the release of the protein.; Probe sonication of the first emulsion was shown to increase encapsulation efficiency of FITC-BSA whereas the polymer ratio of 1:3 was shown to localize the FITC-BSA in the inner core. Therefore these steps were incorporated into the technique. In vitro degradation of these spheres can be broken down into two phases, the first phase lasting for 40 days representing mostly the PLGA degradation after which the microsphere structure collapses and a much slower second phase mostly represented by the PLLA degradation.; Sustained delivery of insulin indicted Type I diabetes and olanzapine indicated for schizophrenia was shown in diabetic and normal rats respectively using double walled spheres. Double walled spheres made form PLLA and PLGA show great promise as a drug delivery platform for several applications that require sustained delivery.