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Evaluation of β-cyclodextrin-modified gemini surfactant-based delivery systems in melanoma models

Authors Michel D, Mohammed-Saeid W, Getson H, Roy C, Poorghorban M, Chitanda JM, Verrall R, Badea I

Received 31 August 2016

Accepted for publication 15 October 2016

Published 12 December 2016 Volume 2016:11 Pages 6703—6712

DOI https://doi.org/10.2147/IJN.S121156

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Thomas Webster


Deborah Michel,1 Waleed Mohammed-Saeid,1 Heather Getson,1 Caitlin Roy,1 Masoomeh Poorghorban,1 Jackson M Chitanda,2 Ronald Verrall,2 Ildiko Badea1

1Drug Design and Discovery Research Group, College of Pharmacy and Nutrition, 2Department of Chemistry, University of Saskatchewan, Saskatoon, SK, Canada

Abstract:
Novel drug delivery systems are developed to improve the biological behavior of poorly soluble drugs and to improve therapeutic outcomes. In melanoma therapy, the goal is efficient drug delivery and mitigation of drug resistance. Melphalan (Mel), a currently used therapeutic agent for melanoma, requires solvent system for solubilization, leading to poor chemical stability. Moreover, drug resistance often renders the drug inefficient in clinical setting. A novel β-cyclodextrin-modified gemini surfactant (CDgemini) delivery system was developed to incorporate Mel in order to improve its physicochemical and biological behavior. Melphalan nanoparticles (Mel-NP) showed optimal particle size in the 200–250 nm range for endocytosis and induced significantly higher cell death compared with Mel (50% of inhibitory concentration [IC50] of 36 µM for the complexes vs 82 µM for Mel). The CDgemini delivery system did not alter the pathway of the cellular death triggered by Mel and caused no intrinsic toxicity to the cells. The Mel-NP complexes induced significant cell death in melanoma cells that were rendered resistant to Mel. These findings demonstrate in principle the applicability of the CDgemini delivery system as safe and efficient alternative to the current melanoma therapy, especially in chemoresistant cases.

Keywords: lipid nanoparticles, anticancer agent, drug resistance, apoptosis, spheroid, zeta potential, flow cytometry

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