Devina Verma and Zeenat Iqbal
Jamia Hamdard, India
Posters & Accepted Abstracts: J Nanomed Nanotechnol
Suboptimal therapeutic outcomes, growing resistance and associated side effects of conventional chemotherapy has led to a growing interest in usage of safer combinations which positively effects the patientâ??s QoL. Developing a nanosystem which can incorporate drugs with juxtaposing physiochemical properties and target the same at the desired tumor site is highly desirable but requires strategic formulatory approach. The current work is aimed at developing a lectin targeted PLGA nanoparticulate system incorporating topotecan and thymoquinone for synergistic anticancer activity and better targetability. Topotecan- thymoquinone nanoparticles (TP-TY NPs) were formulated by double emulsion solvent evaporation method, optimized using central composite design and conjugated with wheat germ agglutinin (WGA) via carbodiimide chemical coupling. WGA-TPTY NPs were subjected to sequential characterization and release kinetic was determined using dialysis bag method. The cytotoxicity and cell uptake of WGA-TPTY NPs was studied in MCF-7 cell line and finally evaluated in Earlich Ascites Carcinoma model. WGA-TPTY NPs had a particle size of 246.7±8.3nm and % entrapment and loading of 58.6±3.6 and 6.52±0.25 respectively for thymoquinone and 42.3±1.2% and 3.6±0.26 for topotecan respectively. The particles had a spherical shape, residual PVA of 4.22% and zeta potential of -1.02mV. In vitro release study revealed a sustained release pattern of both the drugs for 96 hours. The conjugated NPs showed a marked reduction in IC50 and higher cellular uptake as compared to plain drugs and the unconjugated counterpart. Further, a significant reduction in the tumor volume was observed with better hematological profile indicating the efficacy and safety of the nanoparticles. Conclusively, the developed nanoparticles showed efficient drug loading, better efficacy and safety and potential for tumor targeting. devinaverma12@gmail.com