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Sujay Shah, Asha Patel, Sulabh Patel, Dhananjay Pal, Ashim Mitra; NOVEL AQUEOUS NANOMICELLAR FORMULATIONS CONTAINING FLUOCINOLONE ACETONIDE FOR THE TREATMENT OF POSTERIOR UVEITIS. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1076.
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Diseases like posterior uveitis affect the posterior segment of the eye and can cause partial or total vision loss. Current forms of treatments require administration of high doses to overcome static and dynamic barriers present in the eye. Fluocinolone acetonide (FA) is a highly potent glucocorticoid therapeutic with anti-inflammatory properties. Current therapy involves surgical placement of intra-vitreal implant of FA. This method has several disadvantages like retinal detachment, redness, pain and discomfort - all of which can lead to patient non-compliance. Therefore, the optimum strategy is to develop eye drops of FA. Since FA is very poorly soluble in water, it is difficult to prepare high concentration clear aqueous solution eye drops of FA. Therefore, our aim in this study is to develop aqueous nanomicellar formulations containing FA. Vitamin E TPGS (1K), a surfactant polymer has been utilized to prepare nanomicelles. We also synthesized polymer with higher molecular weight of PEG (2000) (2K). This modified polymer has a very low critical micellar concentration (CMC) which might improve the stability upon tear dilution in eye.
Modified TPGS was synthesized by conjugation D-α- tocopheryl succinate and mPEG having molecular weight of 2000. The product was purified by dialysis method. CMC values were calculated using standard pyrene method. Micelles were prepared by thin film hydration technique. Box-Behnken design was used to optimize the formulation to achieve maximum entrapment and solubility of drug. Size and zeta potential of micelles was measured. Cytotoxicity studies were conducted on corneal and retinal cells.
2K polymer was successfully synthesized with a yield of 65%. The CMC value obtained was 7.28μg/ml which is significantly less than commercially available TPGS 1K. Results showed that solubility of FA maybe increased up to 26 times with newly synthesized 2K polymer. Entrapment efficiency greater than 90% was achieved with 2K polymers. Nanomicelles exhibited very small size (<20nm) and narrow size distribution with both polymers. Cell viability on both corneal (HCEC) and retinal (D407) cells lines was comparable to control.
We have successfully optimized the formulation with respect to entrapment efficiency, aqueous solubility and no cytotoxicity. This could be used as a potential topical eye drop treatment for posterior uveitis.
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