Control of the biodegradation rate of poly(DL-lactide) microparticles intended as chemoembolization materials

There is an interest in polylactide microspheres that biodegrade within a few days, particularly for chemoembolization applications. For this purpose, two poly(DL-lactide) samples of a very different molecular weight have been combined. The basic concept relies upon the capability of the high molecular weight component (M(n) : 65 000) to provide the microspheres with a high mechanical strength, whereas the low molecular weight component (M(n) : 3500) should decrease the particle lifetime dramatically. It has been shown that changing the weight ratio of these two components is an efficient way to control the kinetics of the in vitro degradation of poly(DL-lactide) microspheres on the expected time scale. The microspheres have been prepared by the oil-in-water emulsion/evaporation process, and their final polymer content has been compared to the initial composition of the oil phase. They have also been analyzed by differential scanning calorimetry to know whether the two polymers form a monophase blend or not. Kinetics of the in vitro biodegradation has been estimated from the decrease in molecular weight of the constitutive poly(DL-lactide)s, the time-dependency of the microsphere weight and the observation of changes in the morphology by scanning electron microscopy. Progress in the hydrolysis of the ester groups has also been reckoned from the increasing acidity of the incubation medium and associated with the polymer.