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

Khurana RK 1 , Kumar R 2 , Gaspar BL 3 , Welsby G 4 , Welsby P 4 , Kesharwani P 5 Show all authors , Katare OP 1 , Singh KK 6 , Singh B 7

Affiliations 

  • 1 University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160014, India
  • 2 UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites (Biomedical Sciences), Panjab University, Chandigarh 160014, India
  • 3 Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
  • 4 School of Pharmacy and Biomedical Sciences, Faculty of Clinical and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK
  • 5 Department of Pharmaceutical Technology, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia; Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, UP 226031, India
  • 6 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
  • 7 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
Mater Sci Eng C Mater Biol Appl, 2018 Oct 01;91:645-658.
PMID: 30033299 DOI: 10.1016/j.msec.2018.05.010

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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