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

A laboratory-scale method of producing micron-sized hollow microcapsules fr om a biodegradable polymer such as 50/50 poly(D,L-lactide-co-glycolide) (PL GA), for use as a diagnostic ultrasound contrast agent, was developed. The technique involved microencapsulation of a volatile solid core material, an d subsequent sublimation of the core to leave a hollow microsphere. A core material, such as ammonium carbonate, was ground to a suitable size distrib ution and encapsulated by a modified solvent evaporation or coacervation te chnique. This study investigated process parameters to produce diagnostical ly viable microcapsules by these two encapsulation methods, such as polymer molecular weight (from 10,000 to 50,000), initial polymer concentration, a gitation method, and stabilizer type. Polymer solution viscosity, polydispe rsity, and agitation rates significantly controlled the mean size of the mi crocapsules. Stabilizers were essential in solvent evaporation, but corrupt ed the morphology of spheres made by coacervation. Zeta potential values of microsphere dispersions revealed differences in surface characteristics be tween both encapsulation methods. Incubation of microcapsules with serum im proved their dispersion in aqueous media. Preliminary in vivo ultrasound st udies with the New Zealand white rabbit model, using color Doppler, showed that the microcapsules gave significant contrast in the right kidney.