pH Sensitive Lipid-Polymer Hybrid Nanoparticles Mediated Delivery of Docetaxel: A Viable Approach for Breast Cancer Therapeutic Intervention Development

Present study was planned for the development of pH sensitive lipid polymer hybrid nanoparticles (pHS-LPHNPs) loaded with docetaxel (DTX) for guided and target specific cytosolic-delivery delivery of docetaxel (DTX). pHS-LPHNPs were formulated to entrap DTX by self-assembled nano-precipitation technique and characterised with respect to zeta potential, particle-size, entrapment efficiency, PDI as well as invitro drug release. The cell viability, apoptosis, cellular-uptake, pharmacokinetics, bio-distribution in vital organs, % changes in tumour volume and survival of breast cancer bearing animals were used for the evaluation of efficacy of the formulation. In-vitro studies showed increased cytotoxicity at lower IC50 and better cellular-uptake of pHS-LPHNPs mediated drug by breast cancer cell lines. We saw the better rate of apoptosis of breast cancer cells via Annexin V/Propidium iodide staining. Moreover, in-vivo studies demonstrated improved pharmacokinetics and targetability with minimum drug circulation in deep-seated organs upon delivery of DTX via pHS-LPHNPs in comparison with LPHNPs-DTX and free DTX. We observed sizeable % reduction in tumour-burden with pHS-LPHNPs-DTXthan that withLPHNPs-DTX &free DTX. In brief, pHS-LPHNPs mediated delivery of DTX exhibited promising approach for developing therapeutic-interventions against breast-cancer.