Innovative film-forming lyotropic crystal gel co-loaded with Pimecrolimus and Wrightia tinctoria oil for synergistic psoriasis therapy and patient acceptance.

Psoriasis is a chronic immune-mediated inflammatory skin disease affecting millions of individuals worldwide. Pimecrolimus (PMS), a calcineurin inhibitor, suppress T-cell activation thereby interrupting the inflammatory cascade in psoriasis. However, its poor aqueous solubility limits topical delivery. Wrightia tinctoria oil (WTO), a traditionally used herbal remedy, is anticipated to act synergistically with PMS in ameliorating psoriatic inflammation. Thus, the present study aimed to harness the potential of PMS and WTO by developing WTO PMS co-loaded liquid lyotropic crystals (LLC) incorporated into film forming gel (FFG) for enhanced solubilization, skin permeation and therapeutic performance. WTO PMS co-loaded LLC exhibited a mean particle size of 173 ± 4 nm, polydispersity index of 0.225 ± 0.03, and zeta potential of -29.6 mV. In vitro drug release studies demonstrated a sustained release pattern across the dialysis membrane. The LLCs were further incorporated into FFG base, which exhibited shear-thinning and viscoelastic behaviour, thermal stability (activation energy: 1.414 kJ/mol), bioadhesive strength (0.121 ± 0.04 kg) and sustained drug release profile. Ex vivo permeation studies revealed a 12-fold increase in drug flux and a 2.5-fold enhancement in skin retention from FFG LLC compared to pure drug in FFG base. In vivo anti-psoriatic evaluation demonstrated marked lesion recovery, which was supported by histopathological observations and downregulation of inflammatory cytokines. Overall, the WTO-PMS co-loaded LLC-based film-forming gel presents a promising synergistic platform to overcome the solubility barrier of hydrophobic PMS and achieve effective topical management of psoriasis.