Preparation and characterization of 5-fluorouracil-loaded microparticles as biodegradable anticancer drug carriers

Abstract

To provide a device releasing 5-fluorouracil in a controlled manner and injectable into the brain by stereotaxy, biodegradable poly ((+/-)-lactide-co-glycolide) (PLAGA) microparticles were prepared by an emulsion-extraction process. Although the solubility profile of the drug was not suitable for its encapsulation by the aforementioned method, careful choice of process variables allowed significant drug loading, reaching 30%. Thus, the size of the 5-fluorouracil crystals, the organic phase/aqueous phase ratio, the theoretical drug loading and the microparticle size played a predominant role. The microsphere size was adjusted to 20-40 microns by selecting the appropriate PLAGA and polyvinylalcohol concentrations, and the stirring rate of the initial emulsion. It was shown that the microparticle structure depended directly on the experimental conditions governing the precipitation rate of the coating material: two types of microparticles, I and II, were characterized. The morphology of the particles influenced the 5-fluorouracil-release patterns, as did other process parameters, such as the 5-fluorouracil crystal size and the PLAGA concentration. It was possible to sustain the 5-fluorouracil release over 18 days.