Sulforaphane-Loaded Ultradeformable Vesicles as A Potential Natural Nanomedicine for the Treatment of Skin Cancer Diseases.

Maria Chiara Cristiano,Massimo Fresta,Antonia Mancuso,Steven P Nisticò,Betty P Udongo,Roberta Spaccapelo,Donatella Paolino,Francesca Froiio

doi:10.3390/pharmaceutics12010006

Maria Chiara Cristiano, Massimo Fresta + Show 6 more

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https://doi.org/10.3390/pharmaceutics12010006

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Journal: Pharmaceutics	Publication Date: Dec 19, 2019
Citations: 68	License type: CC BY 4.0

Affiliation: Magna Graecia University, University of Perugia

Abstract

Sulforaphane is a multi-action drug and its anticancer activity is the reason for the continuous growth of attention being paid to this drug. Sulforaphane shows an in vitro antiproliferative activity against melanoma and other skin cancer diseases. Unfortunately, this natural compound cannot be applied in free form on the skin due to its poor percutaneous permeation determined by its physico-chemical characteristics. The aim of this investigation was to evaluate ethosomes® and transfersomes® as ultradeformable vesicular carriers for the percutaneous delivery of sulforaphane to be used for the treatment of skin cancer diseases. The physico-chemical features of the ultradeformable vesicles were evaluated. Namely, ethosomes® and transfersomes® had mean sizes <400 nm and a polydispersity index close to 0. The stability studies demonstrated that the most suitable ultradeformable vesicles to be used as topical carriers of sulforaphane were ethosomes® made up of ethanol 40% (w/v) and phospholipon 90G 2% (w/v). In particular, in vitro studies of percutaneous permeation through human stratum corneum and epidermis membranes showed an increase of the percutaneous permeation of sulforaphane. The antiproliferative activity of sulforaphane-loaded ethosomes® was tested on SK-MEL 28 and improved anticancer activity was observed in comparison with the free drug.

Highlights

Sulforaphane (1-isothiocyanate-(4R)-(methylsulfinyl)-butane) is a natural dietary isothiocyanate.It is an enzymatic product obtained from the reaction between myrosinase and glucopharanin, a4-methylsulfinylbutyl glucosinolate contained in cruciferous vegetables, e.g., broccoli, brussel sprouts, and cabbage
Sulforaphane mediates apoptosis and cell cycle arrest; protein kinases, important mediators of cell growth and proliferation, are inactivated by sulforaphane in tumor cells. It promotes the reactive oxygen species (ROS) production leading to DNA damage and activation of the apoptotic mechanism in different cancer cell lines
Deformable vesicles were submitted to light scattering analysis so as to choose the most suitable formulation to be tested in vitro

Summary

Introduction

Sulforaphane (1-isothiocyanate-(4R)-(methylsulfinyl)-butane) is a natural dietary isothiocyanate.It is an enzymatic product obtained from the reaction between myrosinase and glucopharanin, a4-methylsulfinylbutyl glucosinolate contained in cruciferous vegetables, e.g., broccoli, brussel sprouts, and cabbage. Sulforaphane mediates apoptosis and cell cycle arrest; protein kinases, important mediators of cell growth and proliferation, are inactivated by sulforaphane in tumor cells It promotes the reactive oxygen species (ROS) production leading to DNA damage and activation of the apoptotic mechanism in different cancer cell lines. Apoptosis can be induced by death receptor 5, activator protein 1, MAP kinases, or mithocondrial dysfunction, or by suppressing the mechanisms responsible for cellular survival, for example, inhibiting activation of the nuclear factor-kappa B [8,9] Since sulforaphane has these multiple anticancer mechanisms, it is able to inhibit one or more pathways that contribute to malignant transformation and possesses cancer-preventive properties against different tumor diseases [10,11,12], including melanoma [13]

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