Our major objectives for this study are to prepare a topical pluronic lecitin organogel (PLO) formulation of fisetin, a natural dietary polyphenolic agent and our recently characterized more potent synthetic derivatives as effective, topical delivery vehicles, and to characterize their efficacies as safer alternatives for treating cutaneous T cell mediated inflammatory skin disorders (TCSD) with an emphasis on psoriasis. Our study is based on three observations: i) topical application of fisetin solubilized in dimethyl sulfoxide has been shown to alleviate psoriasis-like features in a three-dimensional full thickness reconstituted human skin equivalent model of psoriasis (FTRHSP); ii) fisetin is known to modulate hyper-proliferative and inflammatory responses in chronic conditions; and iii) fisetin analogs have been shown to have anti-proliferative properties in vitro. These formulations may present superior advantage over others with less potential for unwanted, adverse side effects. PLO is an extemporaneous formulation that is non-toxic, non-irritating, non-allergenic and works rapidly with predictable and reproducible effects. The topical route of administration allows the active ingredients to effectively bypass the oral and gastrointestinal systems, thus eliminating first-pass metabolism, bridging bioavailability issues, and avoiding side effects and problems related to the gastrointestinal tract passage. Therefore, fisetin, and its characterized potent derivatives are appropriate study agents for effective topical therapeutic translation. Based on these observations, we hypothesize that the medicated PLO formulation of fisetin and/or its derivatives will provide a successful transdermal delivery of the active ingredient(s) across the skin and increase the active ingredient's permeation ability for systemic absorption to maximize local and systemic therapeutic effects.