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

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, Canad...

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Autores principales:	Michel D, Mohammed-Saeid W, Getson H, Roy C, Poorghorban M, Chitanda JM, Verrall R, Badea I
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	β-cyclodextrin gemini surfactant melanoma lipid nanoparticles melphalan drug resistance apoptosis Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/6c87e1c7f51a4e94ad981cfb6dd09970
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spelling	oai:doaj.org-article:6c87e1c7f51a4e94ad981cfb6dd099702021-12-02T05:06:48ZEvaluation of β-cyclodextrin-modified gemini surfactant-based delivery systems in melanoma models1178-2013https://doaj.org/article/6c87e1c7f51a4e94ad981cfb6dd099702016-12-01T00:00:00Zhttps://www.dovepress.com/evaluation-of-beta-cyclodextrin-modified-gemini-surfactant-based-deliv-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Deborah 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 cytometryMichel DMohammed-Saeid WGetson HRoy CPoorghorban MChitanda JMVerrall RBadea IDove Medical Pressarticleβ-cyclodextringemini surfactantmelanomalipid nanoparticlesmelphalandrug resistanceapoptosisMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 6703-6712 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	β-cyclodextrin gemini surfactant melanoma lipid nanoparticles melphalan drug resistance apoptosis Medicine (General) R5-920
spellingShingle	β-cyclodextrin gemini surfactant melanoma lipid nanoparticles melphalan drug resistance apoptosis Medicine (General) R5-920 Michel D Mohammed-Saeid W Getson H Roy C Poorghorban M Chitanda JM Verrall R Badea I Evaluation of β-cyclodextrin-modified gemini surfactant-based delivery systems in melanoma models
description	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
format	article
author	Michel D Mohammed-Saeid W Getson H Roy C Poorghorban M Chitanda JM Verrall R Badea I
author_facet	Michel D Mohammed-Saeid W Getson H Roy C Poorghorban M Chitanda JM Verrall R Badea I
author_sort	Michel D
title	Evaluation of β-cyclodextrin-modified gemini surfactant-based delivery systems in melanoma models
title_short	Evaluation of β-cyclodextrin-modified gemini surfactant-based delivery systems in melanoma models
title_full	Evaluation of β-cyclodextrin-modified gemini surfactant-based delivery systems in melanoma models
title_fullStr	Evaluation of β-cyclodextrin-modified gemini surfactant-based delivery systems in melanoma models
title_full_unstemmed	Evaluation of β-cyclodextrin-modified gemini surfactant-based delivery systems in melanoma models
title_sort	evaluation of β-cyclodextrin-modified gemini surfactant-based delivery systems in melanoma models
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/6c87e1c7f51a4e94ad981cfb6dd09970
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Evaluation of &beta;-cyclodextrin-modified gemini surfactant-based delivery systems in melanoma models

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