Efficient in vitro and in vivo docetaxel delivery mediated by pH-sensitive LPHNPs for effective breast cancer therapy.

Autor: Jadon RS; School of Studies in Pharmaceutical Sciences, Jiwaji University, Gwalior, MP, 474002, India; Divine International Group of Institutions, Gwalior, MP, India., Sharma G; University Institute of Pharmaceutical Sciences, UGC Centre for Advanced Studies, Panjab University, CH, 160014, India., Garg NK; University Institute of Pharmaceutical Sciences, UGC Centre for Advanced Studies, Panjab University, CH, 160014, India., Tandel N; Institute of Science, Nirma University, Ahmedabad, GJ, 382481, India., Gajbhiye KR; Poona College of Pharmacy, Bharati Vidyapeeth, Pune, MH, 411038, India., Salve R; Nanobioscience, Agharkar Research Institute, Pune, MH, 411004, India., Gajbhiye V; Nanobioscience, Agharkar Research Institute, Pune, MH, 411004, India., Sharma U; Department of Community Medicine & School of Public Health, PGIMER Chandigarh, India., Katare OP; University Institute of Pharmaceutical Sciences, UGC Centre for Advanced Studies, Panjab University, CH, 160014, India., Sharma M; School of Studies in Pharmaceutical Sciences, Jiwaji University, Gwalior, MP, 474002, India. Electronic address: manojdrde@gmail.com., Tyagi RK; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Centre (VUMC), 2215 Garland Avenue, 1075 Lab Suite MRB IV, Nashville, TN, 37232, USA; Biomedical Parasitology and Nano-immunology Lab, CSIR Institute of Microbial Technology (IMTECH), CH, India. Electronic address: rajeevtyagi@imtech.res.in.
Jazyk: angličtina
Zdroj: Colloids and surfaces. B, Biointerfaces [Colloids Surf B Biointerfaces] 2021 Jul; Vol. 203, pp. 111760. Date of Electronic Publication: 2021 Apr 11.
DOI: 10.1016/j.colsurfb.2021.111760
Abstrakt: 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 IC 50 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 pHS-LPHNPs-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.
(Copyright © 2021. Published by Elsevier B.V.)
Databáze: MEDLINE
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