Transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel

Dominique Pepe,1 Vanessa FM Carvalho,2 Melissa McCall,1 Débora P de Lemos,2 Luciana B Lopes1,2 1Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA; 2Department of Pharmacology, Institute of Biomedical Sciences, University of S&atild...

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Autores principales:	Pepe D, Carvalho VFM, McCall M, de Lemos DP, Lopes LB
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	microemulsion nanocarriers protein transduction domains paclitaxel skin transdermal Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a67d183f0ae641fb801024a5512509c5
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spelling	oai:doaj.org-article:a67d183f0ae641fb801024a5512509c52021-12-02T05:08:58ZTransportan in nanocarriers improves skin localization and antitumor activity of paclitaxel1178-2013https://doaj.org/article/a67d183f0ae641fb801024a5512509c52016-05-01T00:00:00Zhttps://www.dovepress.com/transportan-in-nanocarriers-improves-skin-localization-and-antitumor-a-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Dominique Pepe,1 Vanessa FM Carvalho,2 Melissa McCall,1 Débora P de Lemos,2 Luciana B Lopes1,2 1Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA; 2Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil Abstract: In this study, the ability of nanocarriers containing protein transduction domains (PTDs) of various classes to improve cutaneous paclitaxel delivery and efficacy in skin tumor models was evaluated. Microemulsions (MEs) were prepared by mixing a surfactant blend (polyoxyethylene 10 oleoyl ether, ethanol and propylene glycol), monocaprylin, and water. The PTD transportan (ME-T), penetratin (ME-P), or TAT (ME-TAT) was added at a concentration of 1 mM to the plain ME. All MEs displayed nanometric size (32.3–40.7 nm) and slight positive zeta potential (+4.1 mV to +6.8 mV). Skin penetration of paclitaxel from the MEs was assessed for 1–12 hours using porcine skin and Franz diffusion cells. Among the PTD-containing formulations, paclitaxel skin (stratum corneum + epidermis and dermis) penetration at 12 hours was maximized with ME-T, whereas ME-TAT provided the lowest penetration (1.6-fold less). This is consistent with the stronger ability of ME-T to increase transepidermal water loss (2.4-fold compared to water) and tissue permeability. The influence of PTD addition on the ME irritation potential was assessed by measuring interleukin-1α expression and viability of bioengineered skin equivalents. A 1.5- to 1.8-fold increase in interleukin-1α expression was induced by ME-T compared to the other formulations, but this effect was less pronounced (5.8-fold) than that mediated by the moderate irritant Triton. Because ME-T maximized paclitaxel cutaneous localization while being safer than Triton, its efficacy was assessed against basal cell carcinoma cells and a bioengineered three-dimensional melanoma model. Paclitaxel-containing ME-T reduced cells and tissue viability by twofold compared to drug solutions, suggesting the potential clinical usefulness of the formulation for the treatment of cutaneous tumors. Keywords: microemulsion, nanocarriers, protein transduction domains, paclitaxel, skin, transdermalPepe DCarvalho VFMMcCall Mde Lemos DPLopes LBDove Medical Pressarticlemicroemulsionnanocarriersprotein transduction domainspaclitaxelskintransdermalMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 2009-2019 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	microemulsion nanocarriers protein transduction domains paclitaxel skin transdermal Medicine (General) R5-920
spellingShingle	microemulsion nanocarriers protein transduction domains paclitaxel skin transdermal Medicine (General) R5-920 Pepe D Carvalho VFM McCall M de Lemos DP Lopes LB Transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel
description	Dominique Pepe,1 Vanessa FM Carvalho,2 Melissa McCall,1 Débora P de Lemos,2 Luciana B Lopes1,2 1Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA; 2Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil Abstract: In this study, the ability of nanocarriers containing protein transduction domains (PTDs) of various classes to improve cutaneous paclitaxel delivery and efficacy in skin tumor models was evaluated. Microemulsions (MEs) were prepared by mixing a surfactant blend (polyoxyethylene 10 oleoyl ether, ethanol and propylene glycol), monocaprylin, and water. The PTD transportan (ME-T), penetratin (ME-P), or TAT (ME-TAT) was added at a concentration of 1 mM to the plain ME. All MEs displayed nanometric size (32.3–40.7 nm) and slight positive zeta potential (+4.1 mV to +6.8 mV). Skin penetration of paclitaxel from the MEs was assessed for 1–12 hours using porcine skin and Franz diffusion cells. Among the PTD-containing formulations, paclitaxel skin (stratum corneum + epidermis and dermis) penetration at 12 hours was maximized with ME-T, whereas ME-TAT provided the lowest penetration (1.6-fold less). This is consistent with the stronger ability of ME-T to increase transepidermal water loss (2.4-fold compared to water) and tissue permeability. The influence of PTD addition on the ME irritation potential was assessed by measuring interleukin-1α expression and viability of bioengineered skin equivalents. A 1.5- to 1.8-fold increase in interleukin-1α expression was induced by ME-T compared to the other formulations, but this effect was less pronounced (5.8-fold) than that mediated by the moderate irritant Triton. Because ME-T maximized paclitaxel cutaneous localization while being safer than Triton, its efficacy was assessed against basal cell carcinoma cells and a bioengineered three-dimensional melanoma model. Paclitaxel-containing ME-T reduced cells and tissue viability by twofold compared to drug solutions, suggesting the potential clinical usefulness of the formulation for the treatment of cutaneous tumors. Keywords: microemulsion, nanocarriers, protein transduction domains, paclitaxel, skin, transdermal
format	article
author	Pepe D Carvalho VFM McCall M de Lemos DP Lopes LB
author_facet	Pepe D Carvalho VFM McCall M de Lemos DP Lopes LB
author_sort	Pepe D
title	Transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel
title_short	Transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel
title_full	Transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel
title_fullStr	Transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel
title_full_unstemmed	Transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel
title_sort	transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/a67d183f0ae641fb801024a5512509c5
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_version_	1718400613030559744

Transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel

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