Intravitreal galactose conjugated polymeric nanoparticles of etoposide for retinoblastoma

Abstract

Abstract Retinoblastoma is a primary intraocular malignancy of childhood arising from the primitive cells of developing retina. Targeted and sustained release chemotherapy offers a great potential in tumor treatment by achieving greater specificity of delivery and improved therapy. Sugar receptors (lectins) are over expressed on retinoblastoma and limited on healthy cells and thus provide a means to achieve drug targeting. Therefore, the objective of this study was to develop a novel sugar receptor-targeted drug delivery system for retinoblastoma cells using etoposide (ETP) as a model drug. Lactobionic acid (galactose) was attached to the surface amino groups of chitosan (GC) via a carbodiimide reaction. The conjugation was characterized by Fourier transform infrared (FT-IR) and 1H-Nuclear magnetic resonance (1H-NMR). ETP loaded poly(lactide-coglycolide) (PLGA) nanoparticles (NPs) i.e. ENP were prepared by solvent displacement method. The formulated ENPs were further coated with synthesized GC thus giving galactose-chitosan anchored ETP PLGA NPs (i.e. GC-ENP). The NPs showed good entrapment efficiency (∼70%). The physicochemical parameters revealed smooth spherical topology (Transmission Electron Microscopy - TEM) with size range of 150-160 nm (Malvern Nano-ZS Zetasizer), a positive zeta potential (∼25 mV) and in vitro sustained-release (drug release in 32 h). Uptake of GC-ENP (70%) was higher than non-conjugated ENP (40%) in Y-79 cells overexpressing sugar receptors. GC-ENP exhibited higher cytotoxicity and induce greater apoptosis in Y-79 cells when compared with pure ETP. Collectively, these results suggest that galactose conjugated ENP could be potentially useful as a novel drug delivery system for retinoblastoma.