Preparation of biodegradable microspheres encapsulated with Cyclosporine A and evaluation of some factors affecting microsphene properties

ABSTRACT

Poly [D, L lactide-co-glycolide][PLGA] is a biocompatible-biodegradable polymer used as a drug delivery carrier. Also, Cyclosporine A [CyA] is the immunosuppressant that its commercial dosage forms have some disadvantages such as low bioavailability, kidney, liver and neural toxicity and variation of blood concentration after adminstration. The aim of this study was to prepare microspheres containing CyA by using different grades of PLGA.Microspheres were prepared by Solvent Evaporation Method using three grades of PLGA including PLGA [5050], PLGA [6535] and PLGA [8515]. Various characteristics of microspheres such as morphology, size and encapsulation efficiency were evaluated. The mean diameter and particle size distribution of microspheres were measured by particle size analyzer. Release profile of CyA from microspheres was also studied. Complementary studies were carried out by IR [Infrared Spectroscopy] and DSC [Differential Scanning Calorimetery] to evaluate the drug and polymer interaction.SEM studies showed that microspheres were spherical in shape and the small CyA was loaded as islands on the surface of microspheres. Microsphere size was varied between 1 to 25 um with microspheres of PLGA [5050] having the minimum size. Encapsulation efficiency was varied from 75% to 90% and encapsulation efficiency of PLGA [5050] microspheres was different compared to other grades significantly. Profile of release was biphasic, with an initial rapid phase during first 5 days followed by a continuous and slower rate thereafter. Microspheres made from grades 5050 and 8515 showed the highest and the lowest amount of release, respectively. IR spectra for drug, polymer and microsphere did not indicate any chemical interaction between the components of microsphere and DSC thermograms suggested that CyA is present in its amorphous state.In conclusion, in this study suitable microspheres especially with PLGA [5050] were prepared which allow the controlled release of CyA over a prolonged period of time and could be used as a slow release particulate drug deliverysystem and according to microsphere size intact absorption of microspheres after oral administration is expected