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Transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel

Authors Pepe D, Carvalho V, McCall M, de Lemos D, Lopes L

Received 7 October 2015

Accepted for publication 16 January 2016

Published 11 May 2016 Volume 2016:11 Pages 2009—2019


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Dr Thomas Webster

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

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