Development Of Microspheres For Intravitreous Injection Therapy

Microspheres consist of drugs entrapped with a polymer, the drug is dissolved or dispersed through the polymeric matrix. The aim in the development of microspheres has been to obtain long-acting drug depot formulations and specific drug targeting options. Release of drugs from microspheres occurs by several mechanisms, including diffusion through the polymer mixtre and /or through the fluid-filled pores, physical erosion and/or hydrolysis of the polymer, or by a combination of these mechanisms. Treatmente of the vitreoretinal disorders often imclude intraviteous injections to achieve intraocular drug levels within the therapeutical range. However, the risks of complications incease with frequency of intraviteous injections. Controlled drug delivery formulations, offer an excellent alternative to multiple administrations. Microspheres provide an alternative to multiple injections to obtain sustained release of the drug with a single administration.For the sake of continuous delivery of dexamethasone in the intraviteous injection therapy of proliferative vitreoretinopathy, the biodegradable polylactic-co-glycolic acid(PLGA) microspheres loaded with dexamethasone were prepared with an oil-in-water emulsion-solvent evaporation technique. The properties of the microsperes such as the size in diameter, drug-loading capacity, rate of entrapment and the characteristics of the drug release were evaluated. Theresults showed that the average diameter was 4.70 n m ± 1.6 u m. The encapsulation efficiency was 78.8% ± 1.3% and the drug-loading capacity was 15.49% ± 0.31%. 90% of the dexamethasone was released in vitro the microspheres after lOdays by the ways of diffusion and polymeric erosion. The results suggest that the microspheres prepared provided continuous release of dexamethasone.To prepare 5-fluorodeoxyuridine microspheres for intravitreous injection, an oil-in-oil(o/o)emulsion -solvent evaporation method was used. The microspheres were observed under light microscope and the drug-loading capacity as well as the rate of entrapment and the characteristics of the drug release were evaluated. The microsphere was 8.52 jam in diameter with the drug-loading capacity7.66%±0.06% and the entrapment rate 75.96%±0.80%. The initial drug burst within one hour was observed 60% of the total amounts. As some drug adsorbed on the surface, the dissolution profile of the microsphere exhibited a burst of drug during initial stage. During the later stage, the drug release rate was determined by the diffusion of drug from the matrix and the erosion of the polymer. The results suggested the method of oil-in-oil emulsion-solvent evaporation method is enough to prepare 5-Fudr microspheres for intravitreous injection.Animal study was conducted to evaluate the therapeutic effect of intravitreous injection of dexamethasone microspheres. Animal model of proliferative vitreoretinopathy (PVR) was established by injection of rabbit fibroblast into the vitreous. The safety of microspheres injection was tested firstly. 0.1 ml( 10 mg) empty PLGA microspheres as well as dexanmethasone PLGA microspheres were injected separately into the vitreous of 4 rabbits. 28 days later indirect retinoscope and histological examination of the retina revealed normal. Twelve rabbits were then divided into 3 groups (4 for each group) rplacebo microspheres (group A, negative control ) , dexanmethasone (group B, positive control) and dexanmethasone PLGA microspheres (group C, test group). 0.1 ml of each preparations were injected separately into the vitreous after in the injection of rabbit fibroblast. At 1,4,7,14 and 28 days after the treatment, the fundus of the rabbits were examined by slit-lamp microscope and indirect retinoscope.Fastenberg score system were used to describe the change in the vitreous. The results showed that 28 days after the treatment, PVR score was 3.8 in the group A, 3.0 in group B and 1.9 in group C. Significance in the PVR formation was observed between group C and group A (/*<0.01), group C and group B (PO.05) but not group A and group B (P>0.05). The result suggests that dexanmethasone PLGA microspheres are effective and safe in the control of PVR development.