A new plant-based drug delivery platform based on alkyl polyglucosides and β-sitosterol nanovesicles for topical delivery

• Novel nanovesicles without animal-derived components have been developed. • These stable nanovesicles are formed by the self-assembly of β-sitosterol, lauryl glucoside and lauryl glucose carboxylate using the single-step DELOS methodology. • Tocopherol as a hydrophobic model molecule is efficiently loaded in the nanovesicles (49 ± 12 %) maintaining its antioxidant function. • This new nanovesicles are biocompatible with the skin, as evaluated in a 3D epidermal in vitro model. • They enhance the ex vivo skin permeation of a hydrophobic fluorescent probe in terms of time and depth through the epidermis. The finding of new vesicular systems is a challenging process that depends on different factors such as the components used, the interactions between them or the dispersant media. Our objective was to develop a new vesicular delivery system formed by self-assembly of β-Sitosterol (Sit), Lauryl Glucoside (LGL) and Lauryl Glucose Carboxylate (LGC) molecules, all plant-based, biodegradable and biocompatible components. Nanovesicles (NVs) with different molar ratios of Sit, LGL and LGC were prepared using a single step method named DELOS, and characterized by dynamic light scattering, cryo-electron microscopy and small-angle X-ray scattering. Antioxidant compound α-tocopherol (TCP) was integrated in the NVs showing their potential to nanoformulate hydrophobic payloads. Finally, in vitro biocompatibility assays with reconstructed human epidermis and ex vivo skin retention studies using multiphoton microscopy and NVs labelled with Nile Red (NR) were carried out. As a result of this work, a new platform of NVs has been obtained by the self-assembly of Sit, LGL and LGC, obtaining vesicular systems with tunable physicochemical properties in terms of size (130 – 220 nm), surface charge ((-70) – (-40) mV) and lamellarity (unilamellar and multilamellar vesicles), when the carbon chain of the alkyl polyglucoside was >12. The vesicles could efficiently integrate TCP, proving their potential role as delivery systems and maintaining its antioxidant activity after loading. Finally, they also showed biocompatibility with the skin and improved the permeability of the poorly water-soluble molecule NR in terms of time and depth through the epidermis. Overall, the results of this work point to the successful development of an attractive platform based on stable and homogeneous nanovesicles composed of plant-derived ingredients for topical delivery.