Clathrin-mediated endocytic uptake of PUFA enriched self-nanoemulsifying lipidic systems (SNELS) of an anticancer drug against triple negative cancer and DMBA induced preclinical tumor model.

Autor: Khurana RK; University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160014, India., Kumar R; UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites (Biomedical Sciences), Panjab University, Chandigarh 160014, India., Gaspar BL; Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India., Welsby G; School of Pharmacy and Biomedical Sciences, Faculty of Clinical and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK., Welsby P; School of Pharmacy and Biomedical Sciences, Faculty of Clinical and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK., Kesharwani P; Department of Pharmaceutical Technology, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia; Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, UP 226031, India., Katare OP; University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160014, India., Singh KK; School of Pharmacy and Biomedical Sciences, Faculty of Clinical and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK. Electronic address: ksingh1@uclan.ac.uk., Singh B; University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160014, India; UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites (Biomedical Sciences), Panjab University, Chandigarh 160014, India. Electronic address: bsbhoop@pu.ac.in.
Jazyk: angličtina
Zdroj: Materials science & engineering. C, Materials for biological applications [Mater Sci Eng C Mater Biol Appl] 2018 Oct 01; Vol. 91, pp. 645-658. Date of Electronic Publication: 2018 May 04.
DOI: 10.1016/j.msec.2018.05.010
Abstrakt: The current studies envisage unravelling the underlying cellular internalisation mechanism of the systematically developed docetaxel (DTH) polyunsaturated fatty acid (PUFA) enriched self-nanoemulsifying lipidic micellar systems (SNELS). The concentration-, time- and cytotoxicity-related effects of DTH-SNELS on triple negative breast cancer (TNBC) MDA-MB-231 and non-TNBC MCF-7 cell lines were assessed through Presto-blue assay. Subsequently, rhodamine-123 (Rh-123) loaded SNELS were employed for evaluating their internalisation through flow cytometry and fluorescence microscopy, establishing it to be "clathrin-mediated" endocytic pathway. Apoptosis assay (65% cell death) and cell cycle distribution (47% inhibition at G2/M phase) further corroborated the cytotoxicity of DTH-SNELS towards cancerous cells. Biodistribution, histopathology and haematology studies indicated insignificant toxicity of the optimized formulation on vital organs. Preclinical anticancer efficacy studies using 7,12-dimethylbenzantracene (DMBA)-induced model construed significant reduction in breast tumor-volume. Overall, extensive in vitro and in vivo studies indicated the intracellular localization and cytotoxicity, suggesting DTH-SNELS as promising delivery systems for breast tumor therapeutics including TNBC.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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