Preparation and characterization of hollow microcapsules for use as ultrasound contrast agents

Abstract

A laboratory-scale method of producing micron-sized hollow microcapsules from a biodegradable polymer such as 50/50 poly(D,L-lactide-co-glycolide) (PLGA), for use as a diagnostic ultrasound contrast agent, was developed. The technique involved microencapsulation of a volatile solid core material, and subsequent sublimation of the core to leave a hollow microsphere. A core material, such as ammonium carbonate, was ground to a suitable size distribution and encapsulated by a modified solvent evaporation or coacervation technique. This study investigated process parameters to produce diagnostically viable microcapsules by these two encapsulation methods, such as polymer molecular weight (from 10,000 to 50,000), initial polymer concentration, agitation method, and stabilizer type. Polymer solution viscosity, polydispersity, and agitation rates significantly controlled the mean size of the microcapsules. Stabilizers were essential in solvent evaporation, but corrupted the morphology of spheres made by coacervation. Zeta potential values of microsphere dispersions revealed differences in surface characteristics between both encapsulation methods. Incubation of microcapsules with serum improved their dispersion in aqueous media. Preliminary in vivo ultrasound studies with the New Zealand white rabbit model, using color Doppler, showed that the microcapsules gave significant contrast in the right kidney.