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Sujay J Shah, Sulabh Patel, Ashaben Patel, Ashim K Mitra; Novel Targeted Fluocinolone Acetonide loaded aqueous micelles for the treatment of Posterior Uveitis . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5030. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Diseases of the posterior segment of the eye like posterior uveitis pose a formidable challenge to drug delivery because of the various dynamic and static barriers present in the eye. Current treatment options are intravitreal implants or injections which are not patient compliant. Therefore, the objective of our research project is to develop clear aqueous fluocinolone acteonide (FA) loaded micelles using Vitamin E TPGS (1K), for treatment of posterior uveitis.
Modified TPGS was synthesized by conjugation of D-α- tocopheryl succinate with mPEG having molecular weight of 2000 (2K). Targeted polymer was synthesized by coupling of folic acid to the polymer. The products 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. Quantitative uptake of [(3)H] Folic acid in presence of targeted and non-targeted micelles was studied on D407 retinal cell line with [(3)H] Folic acid as control. Quantitive uptake of fluocinolone acetonide loaded targeted and non-targeted micelles was studied on D407 retinal cell line. Effect of targeted micelles was shown using confocal microscopy.
Modified and targeted polymer was successfully synthesized. The CMC value obtained was 9.44μg/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. Uptake of [(3)H] Folic acid in presence of targeted micelles was less than that of control and non-targeted micelles. Confocal microscopy studies showed increased internalization of targeted micelles as compared to non-taregeted micelles.
Folic acid conjugated Vitmain E TPGS was successfully synthesized. Highly hydrophobic drugs like FA can be formulated into clear aqueous eye drops. Folic acid targeted micelles can be utilized to efficiently deliver drugs to retinal and other ocular tissues.
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