DEVELOPMENT OF BIODEGRADABLE MICROSPHERES AND NANOSPHERES FOR THE CONTROLLED-RELEASE OF CYCLOSPORINE-A

With the aim to develop a new controlled release dosage form of administration for cyclosporin A (CyA), several formulations of CyA-loaded microspheres and nanospheres based on poly(DL-lactide-co-glycolide) (PLGA) were designed. Microspheres and nanospheres, prepared by the solvent evaporation process, were characterized with respect to morphology, size distribution, drug content, internal structure and in vitro drug release. The micro- and nanospheres designed displayed various sizes (from 0.2 to 30 mum), spherical shape and smooth surface. The loading capacity was high for all formulations although it was influenced by the microsphere size. Results obtained by reversed-phase high-performance liquid chromatography, gel-permeation chromatography, differential scanning calorimetry, X-ray powder diffraction and Fourier transform infrared spectroscopy revealed that the peptide forms a molecular dispersion in the co-polymer matrix and no chemical interaction between co-polymer and drug occurs. Release profiles of CyA from the microspheres developed displayed a biphasic shape. The duration and intensity of each phase were affected by the microsphere size and the molecular weight of PLGA. Consequently, using PLGA it is possible to design micro- and nanospheres which allow the controlled release of CyA over a prolonged period of time. This may represent an interesting approach to provide therapeutic levels of the drug for extended periods of time.