Development of biotin decorated Olaparib loaded cationic lipopolymeric hybrid nanoparticle and evaluation of its anticancer effect and pharmacokinetics for triple negative breast cancer

Abstract

Olaparib is a Poly(ADP-ribose) polymerase inhibitor, established for treatment of various cancer. Owing to its poor bioavailability, shorter biological half-life and 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 nanoparticle system for Olaparib was prepared using single-step emulsification followed by solvent evaporation method to enhance the intracellular uptake and pharmacokinetics 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 +30 mV. 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 IC50 of Olaparib by 7.6-fold times in St/Biotin@OLA-LPHNs in 4T1 cell line against free 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 significant apoptosis 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 biocompatible to biological system. In conclusion, in the present study, the developed Olaparib loaded lipo-polymeric nanoparticles demonstrated great potential for controlled release and have opened avenues for developing an effective formulation for improving anticancer effect against triple negative breast cancer.