Ethosomes and Transethosomes for Mangiferin Transdermal Delivery

Abstract

Mangiferin is a natural glucosyl xanthone with antioxidant and anti-inflammatory activity, making it suitable for protection against cutaneous diseases. In this study ethosomes and transethosomes were designed as topical delivery systems for mangiferin. A preformulation study was conducted using different surfactants in association with phosphatidylcholine. Vesicle dimensional distribution was monitored by photon correlation spectroscopy, while antioxidant capacity and cytotoxicity were respectively assessed by free radical scavenging analysis and MTT on HaCaT keratinocytes. Selected nanosystems were further investigated by cryogenic transmission electron microscopy, while mangiferin entrapment capacity was evaluated by ultracentrifugation and HPLC. The diffusion kinetics of mangiferin from ethosomes and transethosomes evaluated by Franz cell was faster in the case of transethosomes. The suitability of mangiferin-containing nanovesicles in the treatment of skin disorders related to pollutants was investigated, evaluating, in vitro, the antioxidant and anti-inflammatory effect of ethosomes and transethosomes on human keratinocytes exposed to cigarette smoke as an oxidative and inflammatory challenger. The ability to induce an antioxidant response (HO-1) and anti-inflammatory status (IL-6 and NF-kB) was determined by RT-PCR and immunofluorescence. The data demonstrated the effectiveness of mangiferin loaded in nanosystems to protect cells from damage. Finally, to gain insight into the keratinocytes’ uptake of ethosome and transethosome, transmission electron microscopy analyses were conducted, showing that both nanosystems were able to pass intact within the cells.

Lipid-Based Nanosystems as a Tool to Overcome Skin Barrier

“…As shown in Figure 4, TEM analysis confirmed the uptake of ethosomes within fibroblasts [74]. The morphology of the vesicles is comparable to that obtained by cryo-TEM visualization reported in Figure 2, where an external phosphatidylcholine bilayer and an inner core are evident.…”

“…In particular, the optimized formulation was nanosized, characterized by good entrapment efficiencies, and showed better penetration across rat’s skin as compared to the control solution, indicating a good potential of this LBN as drug carrier for dermal delivery of fisetin [ 84 ]. On the other hand, Sguizzato et al demonstrated that transethosomes and ethosomes are able to deliver the natural antioxidant mangiferin to the target cell, enhancing the keratinocyte antioxidant defense status, while protecting from the cutaneous ox-inflammatory damage induced by cigarette smoke ameliorating the drug solubility and delivery [ 74 ]. Moreover, the study showed the presence of intact vesicles of both ethosomes and transethosomes within keratinocytes, despite the need for in vivo experiments to clarify the mechanism of vesicle disaggregation within the cells and how these LBNs interact with the skin.…”

“Plurethosome” as Vesicular System for Cutaneous Administration of Mangiferin: Formulative Study and 3D Skin Tissue Evaluation

“…Notably, due to its antioxidant, antiapoptotic, and antiinflammatory potential, MG has been proposed in the treatment of cutaneous diseases such as contact dermatitis and psoriasis [ 11 , 16 ]. Notwithstanding its therapeutic potential, MG is characterized by scarce water solubility and low bioavailability, requiring advanced drug delivery systems for its administration [ 17 , 18 ]. In this respect, vesicular nanosystems could represent a smart technological strategy for MG application and delivery through the skin.…”

“…Ethanol presence is crucial, since on one hand, it confers softness and malleability to the PC vesicle, while on the other, it exerts a penetration enhancer effect, promoting the ethosome passage through the skin. The addition of surfactants to PC in ethosome composition has led to the development of transethosome, a second generation of ethosome, which is characterized by even more flexible vesicles with major transdermal potential [ 18 , 24 , 25 ]. The uptake of ethosome and transethosome within keratinocytes has been recently demonstrated by transmission electron microscopy analyses, confirming their penetration enhancer ability and their capability to deliver drugs within cells [ 18 , 25 ].…”

“…The addition of surfactants to PC in ethosome composition has led to the development of transethosome, a second generation of ethosome, which is characterized by even more flexible vesicles with major transdermal potential [ 18 , 24 , 25 ]. The uptake of ethosome and transethosome within keratinocytes has been recently demonstrated by transmission electron microscopy analyses, confirming their penetration enhancer ability and their capability to deliver drugs within cells [ 18 , 25 ]. Since the oxidative stress mediators can alter the expression of stratum corneum lipid components, the cutaneous administration of lipid vesicular nanosystems appears particularly interesting in the treatment of skin pathologies, offering the possibility to restore the lipid depletion caused by environmental pollutants [ 26 ].…”