P. Narayan et Ma. Wheatley, Preparation and characterization of hollow microcapsules for use as ultrasound contrast agents, POLYM ENG S, 39(11), 1999, pp. 2242-2255
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.