Efficacy evaluation of carboplatin -etoposide Co-loaded PLGA microparticles for subconjunctival chemotherapy in retinoblastoma

Abstract

Systemic chemotherapy for retinoblastoma comes with various haematological side effects, hence, require newer treatment approaches. This study developed carboplatin (CPT) and etoposide (ETP) loaded biodegradable PLGA microparticles as a combination therapy for extended action decreasing frequency of administration. CPT and ETP loaded PLGA microparticles (CE-MIP) were prepared by emulsification-spray drying technique. The optimized drug loaded PLGA microparticles were characterized for particle size (3–14 μm), zeta potential (−23.0 to −34.2 mV), entrapment efficiency (ETP - >80 % & CPT - >60 %) and in vitro release (CPT – 4 h & ETP – 72 h). In vitro cytotoxicity studies of CE-MIP showed greater anti-cancer effect (25.33 % cell viability) compared to plain drug mixture (38.56 % cell viability) in Y-79 cells. In WERI-Rb cell lines, the CE-MIP and plain drug mixture at 100 μM showed percent cell viability as 37.82 % and 66.08 % respectively. In the soft agar assay, the CE-MIP treatment demonstrated a significant reduction in the number of colonies (∼50 % reduction) formed compared to control. In orthotropic mouse model of retinoblastoma, the apoptotic effect of subconjunctival CE-MIP (15.7 %) was greater compared to control (7.9 %). Mean tumor burden of CE-MIP treated eyes was significantly smaller compared to the untreated control eyes showing the anti-tumor efficacy of developed CE-MIP.