Abstract
Drug delivery systems (DDS) based on poly (lactide-co-glycolide) (PLGA) microspheres and nanospheres have been separately studied in previous works as a means of delivering bioactive compounds over an extended period of time. In the present study, two DDS having different sizes of the PLGA spheres were compared in morphology, drug (dexamethasone) loading efficiency and drug release kinetics in order to investigate their feasibility with regard to production of medical combination devices for orthopedic applications. The loaded PLGA spheres have been produced by the oil-in-water emulsion/solvent evaporation method following two different schemes. Their morphology was assessed by scanning electron microscopy and the drug release was monitored in phosphate buffer saline solution at 37A degrees C for 550 h using high performance liquid chromatography. The synthesis schemes used produced spheres with two different and reproducible size ranges (20 +/- A 10 and 1.0 +/- A 0.4 mu m) having a smooth outer surface and regular shape. The drug loading efficiency of the 1.0 mu m spheres was found to be 11% as compared to just 1% for the 20 mu m spheres. Over the 550 h release period, the larger spheres (diameter 20 +/- A 10 mu m) released 90% of the encapsulated dexamethasone in an approximately linear fashion whilst the relatively small spheres (diameter 1.0 +/- A 0.4 mu m) released only 30% of the initially loaded dexamethasone, from which 20% within the first 25 h. The changes observed were mainly attributed to the difference in surface area between the two types of spheres as the surface texture of both systems was visibly similar. As the surface area per unit volume increases in the synthesis mixture, as is the case for the 1.0 mu m spheres formulation, the amount of polymer-water interfaces increases allowing more dexamethasone to be encapsulated by the emerging polymer spheres. Similarly, during the release phase, as the surface area per unit volume increases, the rate of inclusion of water into the polymer increases, permitting faster diffusion of dexamethasone.