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

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Efficient in vitro and in vivo docetaxel delivery mediated by pH-sensitive LPHNPs for effective breast cancer therapy
 
Creator Jadon, Rajesh Singh
Sharma, Gajanand
Garg, Neeraj
Tandel, Nikunj
Gajbhiye, Kavita
Salve, Rajesh
Gajbhiye, Virendra
Sharma, Ujjawal
Katare, O P
Sharma, Manoj
Tyagi, Rajeev K
 
Subject QR Microbiology
 
Description 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.
 
Publisher Elsevier Science/Academic Press
 
Date 2021-07
 
Type Article
PeerReviewed
 
Relation https://www.sciencedirect.com/science/article/abs/pii/S0927776521002046
http://crdd.osdd.net/open/2698/
 
Identifier Jadon, Rajesh Singh and Sharma, Gajanand and Garg, Neeraj and Tandel, Nikunj and Gajbhiye, Kavita and Salve, Rajesh and Gajbhiye, Virendra and Sharma, Ujjawal and Katare, O P and Sharma, Manoj and Tyagi, Rajeev K (2021) Efficient in vitro and in vivo docetaxel delivery mediated by pH-sensitive LPHNPs for effective breast cancer therapy. COLLOIDS AND SURFACES B-BIOINTERFACES, 203. ISSN 0927-7765