Development Of Surface Charge Modified-Biotin Decorated Olaparib Loaded Lipid-Polymeric Hybrid Nanoparticle and Evaluation of its In-Vitro Anticancer Effect and Pharmacokinetics for Triple Negative Breast Cancer Management

Abstract

Olaparib is a PARP inhibitor, established for treatment of various cancer. Owing to its poor bioavailability, shorter biological half-life and with requirement of frequent dosing of high oral dose, it displays lower therapeutic response and undesired toxicity. Thus, to address these issues, in the present work, a surface charge modified biotinylated lipo-polymeric nanoparticles system for Olaparib was prepared using single-step emulsification followed by solvent evaporation to enhance the intracellular uptake, pharmacokinetic in biological system. The resulting Olaparib loaded lipo-polymeric hybrid nanoparticle exhibited an average particle size of <150 nm with a surface zeta potential of less than +30mV. The release profile of Olaparib loaded lipo-polymeric nanoparticle (OLA-LPHNs, St@OLA-LPHNs and St/Biotin@OLA-LPHNs) indicated a controlled type drug release pattern in comparison to pure Olaparib. In-vitro cytotoxicity of olaparib loaded nanoparticle demonstrated an improvement in half-maximal inhibitory concentrations (IC50) of Olaparib by appx. 8-fold times higher in St/Biotin@OLA-LPHNs in 4T1 cell line against Olaparib. Subsequently, blank nanoparticle showed no cellular death which indicates no significant toxicity of nanocarrier. The apoptosis profile showed that St/Biotin@OLA-LPHNs induced aprox.72 % apoptosis which is significant compared to all other groups i.e., OLA-LPHNs, St@OLA-LPHNs and Olaparib. An improved pharmacokinetic profile was observed in Olaparib loaded lipo-polymeric nanoparticle. Moreover, hematological and histological data revealed that the developed nanoparticles are safe and compatible to biological system. In conclusion, in the present study, the developed loaded lipo-polymeric nanoparticles demonstrating great potential for controlled release and opening avenues for developing an effective formulation for improving anticancer effect in triple negative breast cancer cells.