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S. H. Boddu, J. Gupta, M. R. Chowdhury, A. K. Mitra; Controlled and Targeted Delivery of Doxorubicin for the Treatment of Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5297.
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The objective of this study was to develop a novel folate receptor targeted drug delivery system of doxorubicin (DOX) for the treatment of retinoblastoma (RB).
Biodegradable DOX-loaded poly(d,l-lactide-co-glycolide)-poly(ethylene glycol)-folate (PLGA-PEG-FOL) micelles were prepared with various solvents (DMSO, acetone, and DMF). Effect of solvents on entrapment efficiency, particle size and polydispersity was examined. Effect of thermosensitive gel structure on the release of DOX from the DOX-loaded PLGA-PEG-FOL micelles (DOXM) was also studied.
Qualitative and quantitative uptake studies of DOX and DOXM were carried out in Y-79 cell line. Cytotoxicity studies of DOXM were performed on ARPE-19 cells. Based on size, polydispersity and entrapment efficiency DMF was found to be the most suitable solvent for the preparation of DOXM. Dispersion of DOXM in PLGA-PEG-PLGA gel sustained drug release over a period of two weeks. Uptake of DOX was approximately four times higher with DOXM than DOX in Y-79 cells over-expressing folate receptors. This was further confirmed from the quantitative uptake studies. DOXM exhibited higher cytotoxicity in ARPE-19 cells as compared to DOX.
These polymeric micellar systems suspended in thermosensitive gels may provide sustained and targeted delivery of DOX to RB cells following intravitreal administration.
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