In Vitro and In Vivo Evaluation of an Ocular Delivery System of 5-Fluorouracil Microspheres

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Abstract
Solvent evaporation technique with O/O (oil/oil) emulsion was used to prepare 5-FU (5-fluorouracil) biodegradable microspheres with a polymer of poly(dl-lactide-co-glycolide) combining lecithin as an emulsifier. In vitro drug release was conducted in phosphate buffer with pH 7.4 at 37°C. For in vivo studies, 10 mg of 5-FU microspheres (containing 1 mg of 5-FU) were implanted in the conjunctival area of the rabbit eye. Rabbits were sacrificed at certain time intervals within 7 days after drug application. Samples of aqueous humor and sclera were prepared and analyzed by the high performance liquid chromatography (HPLC) method. The tested 5-FU microsphere contained 10% drug with a mean particle size of 4.4 ± 0.6 μm. The microsphere had a burst release initially (64.9 ± 1.5%), followed by a sustained release; the cumulative release at time points of 1, 10 and 21 days were 71.9 ± 1.9%, 80.1 ± 2.1% and 89.8 ± 2.3%, respectively. For in vivo studies, aqueous humor levels showed a peak at the first sampling point (2 hr), then maintained low levels of 5-FU with a range 0.2-1 μg/mL. Scleral levels were 20-80 μg/mL during a 7-day study. Our results indicate that the prepared 5-FU microsphere provided a long-term release for more than 1 week. The preparation showed no irritation and low toxicity (μg/mL). For application to the eye, it might be potentially useful as a complement drug system in glaucoma filtration surgery.