Formulation characterization and in vitro drug release of hydrogel-thickened nanoemulsions for topical delivery of 8-methoxypsoralen.

Psoralens are lipophilic molecules used to treat skin diseases such as vitiligo and psoriasis, among them, 8-Methoxypsoralen (8-MOP) is the most used to topical skin application. Topical treatment with psoralens can be limited due to insufficient drug penetration into the skin layers. Nanoemulsions have attracted much attention due to their as dermal delivery systems for lipophilic drugs such as 8-MOP. However, nanoemulsions feature low viscosity, which might be unsuitable for topical application. In this work, we produced hydrogel-thickened nanoemulsions using chitosan with different molecular weight as thickening polymer to overcome the low viscosity attributed to nanoemulsions. The aim of this study is to characterize oil-in-water (o/w) nanoemulsions and hydrogel-thickened nanoemulsions based on two different essential oils to in vitro controlled release of 8-MOP. In a previous work, we have reported production, stability and in vitro transdermal release of such formulations. Here, 8-MOP loaded nanoemulsions and hydrogel-thickened nanoemulsions were characterized regarding their morphology, rheological behavior, and in vitro drug release kinetics. Hydrogel-based systems presented a gel-like rheological behavior, being classified as weak gels. 8-MOP in vitro release from hydrogels-based formulations using clove essential oil showed strong dependency chitosan molecular weight. On the other hand, hydrogel-thickened nanoemulsions using sweet fennel oil as inner phase, showed an unexpected pH-dependent behavior not fully understood at the moment. These results need further investigation, nevertheless hydrogel-thickened nanoemulsions revealed to be interesting and complex dermal delivery systems for poorly soluble drugs.

Hydrogel-thickened nanoemulsions based on essential oils for topical delivery of psoralen: Permeation and stability studies.

Nanoemulsions (NE) have attracted much attention due to their as dermal delivery systems for lipophilic drugs such as psoralens. However, NE feature low viscosity which might be unsuitable for topical application. In this work, we produced hydrogel-thickened nanoemulsions (HTN) using chitosan as thickening polymer to overcome the low viscosity attributed to NE. The aim of this study is to develop and characterize oil-in-water (o/w) HTN based on sweet fennel and clove essential oil to transdermal delivery of 8-methoxsalen (8-MOP). NE components (oil, surfactant) were selected on the basis of solubility and droplet size and processed in a high-pressure homogenizer (HPH). Drug loaded NE and HTN were characterized for particle size, stability under storage and centrifugation, rheological behavior, transdermal permeation and skin accumulation. Transdermal permeation of 8-MOP from HTN was determined by using Franz diffusion cell. Transdermal permeation from HTN using clove essential oil showed strong dependency chitosan molecular weight. On the other hand, HTN using sweet fennel oil showed an unexpected pH-dependent behavior not fully understood at the moment. These results need further investigation, nevertheless HTN revealed to be interesting and complex dermal delivery systems for poorly soluble drugs.