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Preparation and evaluation of microemulsion-based transdermal delivery of total flavone of rhizoma arisaematis

Authors Shen LN, Zhang YT, Wang Q, Xu L, Feng NP

Received 19 April 2014

Accepted for publication 25 May 2014

Published 22 July 2014 Volume 2014:9(1) Pages 3453—3464

DOI https://doi.org/10.2147/IJN.S66524

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Li-Na Shen,1 Yong-Tai Zhang,1 Qin Wang,2 Ling Xu,2 Nian-Ping Feng1

1Department of Pharmaceutical Sciences, 2Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China

Abstract: The aims of the present study were to investigate the skin permeation and cellular uptake of a microemulsion (ME) containing total flavone of rhizoma arisaematis (TFRA), and to evaluate its effects on skin structure. Pseudo-ternary phase diagrams were constructed to evaluate ME regions with various surfactants and cosurfactants. Eight formulations of ­oil-in-water MEs were selected as vehicles, and in vitro skin-permeation experiments were performed to optimize the ME formulation and to evaluate its permeability, in comparison to that of an aqueous suspension. Laser scanning confocal microscopy and fluorescent-activated cell sorting were used to explore the cellular uptake of rhodamine 110-labeled ME in human epidermal keratinocytes (HaCaT) and human embryonic skin fibroblasts (CCC-ESF-1). The structure of stratum corneum treated with ME was observed using a scanning electron microscope. Furthermore, skin irritation was tested to evaluate the safety of ME. ME formulated with 4% ethyl oleate (weight/weight), 18% Cremophor EL® (weight/weight), and 18% Transcutol® P, with 1% Azone to enhance permeation, showed good skin permeability. ME-associated transdermal fluxes of schaftoside and isoschaftoside, two major effective constituents of TFRA, were 3.72-fold and 5.92-fold higher, respectively, than those achieved using aqueous suspensions. In contrast, in vitro studies revealed that uptake by HaCaT and CCC-ESF-1 cells was lower with ME than with an aqueous suspension. Stratum corneum loosening and shedding was observed in nude mouse skin treated with ME, although ME produced no observable skin irritation in rabbits. These findings indicated that ME enhanced transdermal TFRA delivery effectively and showed good biocompatibility with skin tissue.

Keywords: microemulsion, transdermal, nanocarrier, cellular uptake

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