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Sujay J Shah, Sulabh P Patel, Ashaben Patel, Ashim K Mitra; Etoposide loaded aqueous micelles for the treatment of Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5267.
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Retinoblastoma is a type of cancer which develops in the retina. Its occurrence is mainly in children below the age of five years. Current treatments include radiation therapy, cryotherapy, laser therapy, chemotherapy and enucleation. These treatments have very severe side effects and if not treated properly, can result in the disease spreading to both eyes and eventually throughout the body. Etoposide, a cytotoxic agent, is one of the agents used for the treatment of retinoblastoma. To overcome the drawbacks associated with the current treatments, a simpler non-invasive form of therapy is extremely necessary. The optimum strategy is to develop aqueous eye drops of etoposide (ET). However, due to poor water solubility of ET, it is difficult to prepare clear aqueous eye drops. Hence, our aim is to formulate ET loaded micelles using Vitamin E TPGS. Folic acid was used as targeting moeity to enhance the bioavailability of drug.
Modified TPGS was synthesized using mPEG(2000) (2K). Vitamin E TPGS was conjugated to folic acid. CMC values were calculated using standard pyrene method. Thin film hydration technique was used to prepare micelles. The formulation was optimized 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. Uptake and release studies were performed. Effect of targeted micelles was shown using confocal microscopy.
2K 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 ET maybe increased up to 25 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 retinal (D407) cells line was comparable to control. Confocal microscopy studies showed increased internalization of drug with targeted micelles.
Folic acid conjugated Vitmain E TPGS was successfully synthesized. Highly hydrophobic drugs like ET can be formulated into clear aqueous eye drops. Using this strategy, unwanted side effects of ET can be eliminated.
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