Abstract
Purpose: :
The aim of this study is to develop a folate receptor targeted drug delivery system for the treatment of retinoblastoma
Methods: :
PLGA nanoparticles (NPs) containing doxorubicin (DOX) were prepared by water/oil/water (W/O/W) emulsion method. Folate-linked nanoparticles (FNPs) of DOX were synthesized and further processed by nanoprecipitation method. Nanoparticles were characterized for size, shape, surface morphology, entrapment efficiency and in vitro drug release. Cell viability studies were carried out on retinal cell line (ARPE-19). Uptake of DOX from pure solutions, NPs and FNPs was qualitatively studied using confocal microscopy. Further quantitative studies were carried on Y-79 cells to compare the cellular internalization of DOX from pure solutions, NPs and FNPs.
Results: :
The entrapment efficiency of DOX in NPs was found to be 35%. Dynamic light scattering data revealed an average particle of 231.8 nm, with a polydispersity value of 0.198. Scanning electron microscopy studies suggest that NPs have uniform size with even surface texture. A biphasic release pattern was observed with an initial rapid release (burst release) followed by sustained release over a period of 96 hours. Cell viability studies on ARPE-19 cells indicated that DOX loaded NPs were more toxic as compared to pure DOX solutions .Confocal images of cells treated with DOX-NPs exhibited higher fluorescence when compared to DOX alone indicating improved cellular intake of DOX. Significant increase in the uptake of DOX was observed with FNPs relative to pure DOX solutions and NPs.
Conclusions: :
DOX containing nanoparticles surface modified with folate receptor undergo receptor mediated endocytosis in cancer cells and can be highly effective in the treatment of retinoblastoma.Supported by National Institute of Health. Grants R01 EY 09171-14 and R01 EY 10659-12
Keywords: retinoblastoma • retina • receptors