Development of Targeted Drug Delivery System for Breast Cancer

Abstract

The present investigation was aimed to develop a targeted co-delivery system of paclitaxel (PAX) and clotrimazole (CLZ) through polycaprolactone (PCL) nanoparticles (NPs). Sialic acid (SA) was employed to acquire active targeting towards breast cancer cells. To accomplish this objective, initially, we optimized the concentration of PAX and CLZ by determining cell viability through MTT assay. CompuSyn software was used to depict the synergistic, additive or antagonist effect of PAX and CLZ in combination. MTT assay and CompuSyn simulations suggest the synergistic activity of PAX and CLZ at 12.5-nM and 25-and#956;M respectively and nominated as PACL. Fluorescent microscopy also supports our finding, where PACL significantly induced nuclear damage in breast cancer cells (MCF-7 and MDA-MB-231). Oxidative stress and nitrogen stress was also aggravated by PACL when compared to individual drug concentration. PACL exhibited significant genotoxicity in cancerous cells whereas glucose uptake was inhibited remarkably through PACL in contrast to individual drug concentration. The second objective was to formulated surface functionalized SA polymeric nanoparticles (SA-PCL-NPs) of PAX. Carbodiimide reaction was exploited to mount SA on the surface of PCL-NPs. Characterisation reveals that SA-PCL-NPs were having spherical morphology with a size range of 151.5 nm to 179.47 nm. SA-PCL-NPs profoundly homed themselves inside the cancer cells and induces apoptosis as suggested by MTT assay and photoluminescence study. newlineWhile in the third objective different variables, that play an integral role in the development of nano-formulation were optimized through response surface methodology (RSM). Box Behnken Design (BBD) was employed to generate 3-dimensional surface plots and further analyzed to study the effect of variables on the particle size (PS) and entrapment efficiency % (%EE). Results suggest that when the optimized concentration of variables will be used, there would be 92.4% chances to get PS of 178.7 nm and %EE of 49.13% and witnessed that