%A Rajesh Singh Jadon
%A Gajanand Sharma
%A Neeraj Garg
%A Nikunj Tandel
%A Kavita  Gajbhiye
%A Rajesh Salve
%A Virendra Gajbhiye
%A Ujjawal Sharma
%A O P Katare
%A Manoj Sharma
%A Rajeev K Tyagi
%O Copyright of this article belongs to Elsevier Science/Academic Press
%J COLLOIDS AND SURFACES B-BIOINTERFACES
%T Efficient in vitro and in vivo docetaxel delivery mediated by pH-sensitive LPHNPs for effective breast cancer therapy
%X The present study was designed to develop pH-sensitive lipid polymer hybrid nanoparticles (pHS-LPHNPs) for specific cytosolic-delivery of docetaxel (DTX). The pHS-LPHNPs-DTX formulation was prepared by self assembled nano-precipitation technique and characterized for zeta potential, particle size, entrapment efficiency, polydispersity index (PDI), and in vitro drug release. In vitro cytotoxicity of pHS-LPHNPs-DTX was assessed on breast cancer cells (MDA-MB-231 and MCF-7) and compared with DTX-loaded conventional LPHNPs and bare DTX. In vitro cellular uptake in MDA-MB-231 cell lines showed better uptake of pHS-LPHNPs. Further, a significant reduction in the IC50 of pHS-LPHNPs-DTX against both breast cancer cells was observed. Flow cytometry results showed greater apoptosis in case of pHS-LPHNPs-DTX treated MDA-MB-231 cells. Breast cancer was experimentally induced in BALB/c female mice, and the in vivo efficacy of the developed pHS-LPHNPs formulation was assessed with respect to the pharmacokinetics, biodistribution in the vital organs (liver, kidney, heart, lungs, and spleen), percentage tumor burden, and survival of breast cancer-bearing animals. In vivo studies showed improved pharmacokinetic and target-specificity with minimum DTX circulation in the deep-seated organs in the case of pHS-LPHNPs-DTX compared to the LPHNPs-DTX and free DTX. Mice treated with pHSLPHNPs-DTX exhibited a significantly lesser tumor burden than other treatment groups. Also, reduced distribution of DTX in the serum was evident for pHS-LPHNPs-DTX treated mice compared to the LPHNPs-DTX and free DTX. In essence, pHS-LPHNPs mediated delivery of DTX presents a viable platform for developing therapeutic-interventions against breast-cancer.
%K Breast cancer; Docetaxel; Cytosolic delivery; Apoptosis; pH sensitive; Lipid polymer hybrid nanoparticles
%V 203
%D 2021
%I Elsevier Science/Academic Press
%L open2698