Ethosomes and Transethosomes as Cutaneous Delivery Systems for Quercetin: A Preliminary Study on Melanoma Cells

Abstract

The present study is aimed to design ethosomes and transethosomes for topical administration of quercetin. To overcome quercetin low bioavailability, scarce solubility and poor permeability that hamper its pharmaceutical use, the drug was loaded in ethosomes and transethosomes based on different concentrations of phosphatidylcholine. Vesicle morphology was studied by cryogenic transmission electron microscopy, while size distribution and quercetin entrapment capacity were evaluated up to 3 months, respectively, by photon correlation spectroscopy and high-performance liquid chromatography. The antioxidant property was studied by photochemiluminescence test. Quercetin release and permeation was investigated in vitro, using Franz cells associated to different membranes. In vitro assays were conducted on human keratinocytes and melanoma cells to study the behavior of quercetin-loaded nano-vesicular forms with respect to cell migration and proliferation. The results evidenced that both phosphatidylcholine concentration and quercetin affected the vesicle size. Quercetin entrapment capacity, antioxidant activity and size stability were controlled using transethosomes produced by the highest amount of phosphatidylcholine. In vitro permeation studies revealed an enhancement of quercetin permeation in the case of transethosomes with respect to ethosomes. Notably, scratch wound and migration assays suggested the potential of quercetin loaded-transethosomes as adjuvant strategy for skin conditions.

Dimethyl Fumarate-Loaded Transethosomes: A Formulative Study and Preliminary Ex Vivo and In Vivo Evaluation

“…Indeed, although both vesicular nanosystems improved DMF stability compared with SOL-DMF, TET 2.7 -DMF enabled a longer control of DMF degradation as well as release kinetics than TET 0.9 -DMF. On the other hand, TET 0.9 -DMF improved DMF in vitro permeability compared with SOL-DMF and TET 2.7 -DMF, suggesting the capability of unilamellar vesicles to enhance DMF diffusion through the membrane, resulting in the highest DMF amount diffused after 24 h. Conversely, the lowest p value calculated in the case of TET 2.7 -DMF indicated a preferential DMF distribution towards the multivesicular vesicles, rather than the membrane, as recently found in the case of TETs designed for quercetin’s transdermal delivery [ 29 ].…”

“…The slight increase in vesicle size due to DMF presence could be related to its possible placement within the TET vesicles, near the head groups of PC at the interface between the glycerol groups and the apolar lipid chains. This positioning can increase the average distance among the PC molecules constituting the bilayer of the vesicles [ 29 ].…”

“…Indeed, it has been observed that unilamellar vesicles often occur in diluted surfactant solutions, while multivesicular and oligovesicular vesicles are usually found in more concentrated ones [ 36 ]. Concerning the influence of PC concentration on vesicle size, different authors described the enlargement of mean diameters due to an increase in PC concentration [ 29 , 37 ]. Specifically, the TET based on PC 2.7% w / w led to multivesicular vesicles, with the Z average value more than doubled compared with that of the unilamellar TET based on PC 0.9% w / w .…”

“…TET preparation was obtained via the cold method [ 29 , 34 ]. Briefly, PC was solubilised in ethanol (30 or 90 mg/mL) under stirring at 750 rpm (IKA RCT basic, IKA ® -Werke GmbH & Co. KG, Staufen, Germany); afterwards, the surfactant T80 was added to the PC solution up to a final 1 % w / v concentration.…”

“…Both for IVRT and IVPT, the samples of dried membranes were rehydrated via immersion in ethanol/water 50:50, v / v for 1 h, before assembling in Franz-type diffusion cells. The receptor compartment of the cell contained 5 mL of ethanol:water 50:50, v / v in order to assure sink conditions, stirred at 500 rpm by a magnetic bar, and thermostated at 32 ± 1 °C during the experiments [ 29 ]. A total of 500 μL of DMF-loaded T-ETO or DMF ethanolic solution (ethanol:water 30:70, v / v ) (DMF 0.5 mg/mL) (SOL-DMF) was placed on the membrane surface in the donor compartment which was sealed afterwards to avoid evaporation.…”