Drug Repurposing with Topical Paclitaxel Delivery for Psoriasis Treatment Enabled by Plant-Inspired Molecular Assembly.

Psoriasis is a chronic inflammatory skin disease, notably characterized by the hyperproliferation of epidermal cells and infiltration of inflammatory cells. Paclitaxel (PTX), beyond its canonical roles in microtubule inhibition and proliferation suppression, has recently garnered increasing attention for its promising therapeutic potential in inflammatory diseases. However, PTX is constrained by its low solubility and poor permeability in topical applications. Based on the applications of Hansen Solubility Parameters in predicting coassembled systems, we herein identified a series of herb-derived small molecules with anti-inflammatory and antioxidant properties that enhance the solubility of PTX. Among them, glycyrrhizic acid not only enhanced the solubility of PTX by nearly 400-fold but also coassembled with PTX to form nanoparticles (PGNs). PGNs featured a high PTX payload (over 30%) and notable skin retention free of excipients and surfactants. PGNs were loaded into a gel, and the resultant PGN@Gel exhibited superior therapeutic efficacy against psoriasis while concomitantly mitigating cutaneous irritation. This coassembly system provides a simple yet efficient approach for solubilizing poorly soluble drugs, thereby broadening the application of PTX-based topical delivery formulations in psoriasis treatment.