Yao xue xue bao = Acta pharmaceutica Sinica

[Intravitreally injectable poly (D, L-Lactide) microspheres containing dexamethasone acetate for sustained release].

PMID 12579978


To prepare and evaluate dexamethasone acetate-loaded poly (d, l-lactide) microspheres for sustained release in vitro and their therapeutic effect on proliferative vitreoretinopathy in vivo. The microspheres were prepared by a solvent evaporation/extraction technique. Properties such as geometric mean diameter, span, drug loading, rate of entrapment and release characteristics were evaluated. Differential scanning calorimetry and X-ray powder diffractometry were used to identify the physical phase of dexamethasone acetate in poly (d, l-lactide) matrix, and safety in vivo was examined. Effect of drug-loaded microspheres on suppression of experimental proliferative vitreoretinopathy was studied in albino rabbit eyes after an intravitreal injection of macrophages. The geometric mean diameter and span of the microspheres were 62.9 microns and 0.92, respectively. Drug loading and rate of entrapment of dexamethasone acetate in microspheres were 17.5% and 86.5%, respectively. Differential scanning calorimetry and X-ray powder diffractometry showed that dexamethasone acetate dispersed uniformly as molecules in poly (d, l-lactide) matrix. Ninety percent of the dexamethasone acetate was released in vitro from dexamethasone acetate after 48 days, while the same amount released from microspheres took 90 days. Storage under 4 degrees C in refrigerator or 25 degrees C in a dessicator at a relative humidity of 75% for 90 days had little effect on the properties of the microspheres. Intravitreal injection of microspheres showed a sustained release and continuous action of dexamethasone acetate for 84 days. After injection of activated macrophages, the groups of blank microspheres and dexamethasone acetate showed proliferation to different extent, while the base of the eye remained clear and no obvious proliferation was observed for the group of microspheres. A significant difference exists between these three groups. Poly (d, l-lactide) microspheres containing dexamethasone acetate is a potentially promising delivery system for the suppression of proliferative vitreoretinopathy.