Thermosensitive hydrogel with nanostructured lipid carriers (NLC) for the topical administration of curcuminoids, resveratrol, and piperine intended for the treatment of psoriasis

Chronic inflammatory conditions, such as psoriasis, require effective therapeutic strategies to manage both local and systemic inflammation. This study aimed to develop a thermosensitive hydrogel (Gel) based on Pluronic F127 and F68, incorporating NLC (Gel-NLC) loaded with anti-inflammatory phytochemicals, such as curcuminoids, resveratrol, and/or piperine, for the topical treatment of psoriasis. Phytochemicals-loaded NLC presented encapsulation efficiency > 90%, particle size values between 39-49 nm, and polydispersity indices <0.211. Compared to curcuminoids and resveratrol from NLC and Gel-NLC, piperine alone or in combination with other phytochemicals showed superior release and transdermal flux both <i>in vitro</i> and <i>ex vivo</i>. Simultaneous encapsulation of resveratrol and piperine significantly decreased the permeation of the former, while an increase in the permeation of piperine was observed when combined with curcuminoids or resveratrol. Confocal microscopy analysis revealed that curcuminoids displayed the highest retention in the skin when encapsulated in NLC as a single agent, followed by resveratrol and piperine. These variations can be attributed to their physicochemical properties. The developed formulations are presented as effective delivery systems that can enhance the availability of these phytochemicals, thereby increasing their anti-inflammatory potential in the treatment of psoriasis.