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.