# Soriasis: From Pathogenesis to Pharmacological and Nano-Technological-Based Therapeutics
## 3 Current Marketed Therapies
It has been dliucated that CYP11A1 initiates the metabolism of vitamin D: from D3 to (OH)nD3 [56]. The main metabolite resulting from a single hydroxylation of D3 by CYP11A1 is 20(OH)D3, but 22(OH)D3 and 17(OH)D3 are also produced [57]. The major dihydroxy and trihydroxy metabolites formed from CYP11A1 hydroxylation of 20 OHD3 include 20,23(OH)2D3, 20,22(OH)2D3, 17,20(OH)2D3, and 17,20,23(OH)3D3 [57]. Moreover, further hydroxylation of CYP11A1-derived metabolites can occur by CYP27B1, CYP24A1, and CYP27A1 [58]. Apart from the well-known mechanism by binding 1\(\alpha\),25(OH)2D3 with VDR, there are different nongenomic associated sites. VDR has an alternative form binding-A-pocket, which leads to rapid nongenomic responses at the cell membrane level [55]. Furthermore, there is a rapid steroid binding protein disulphide-isomerase A3 (PDIA3), which has been identified as an alternative membrane-bound receptor. PDIA3 activates phospholipase C in a G protein-coupled process and results in the production of inositol trisphosphate (IP3) and diacylglycerol. These two cellular messengers mediate the rapid release of calcium from the cellular stores [59]. Recently, ROR\(\gamma\), another nuclear receptor, has been identified as a target for vitamin D, where D3 hydroxderivatives could act as antagonists, regulating some phenotypic expressions with affectation in several immune functions, metabolism, and cerebellar development [59]. Recently, Vitamin D has been studied outside the immune system, with some VDRs localised in the intestinal barrier, regulating intestinal inflammation, autophagy, or gut microbiota [60]. In severe cases, a systemic treatment, sometimes combined with local treatment, is necessary due to the increased extension of the affected surface. Some strategies for enhancing the therapeutic results of the topical treatments, such as using some adjunct agents, such as penetrating or permeating enhancers, or phototherapy, can be employed [61]. It has been demonstrated that monotherapies, which require irregular applications, are not the best options for the optimisation of the treatment adherence [62]. One option for improving the treatment adherence is a combination regime [63], which allows applications in a fixed dose with a low frequency of application [64]. Topical therapies are the backbone of management of psoriasis. They are safe and well-tolerated by the patients. Currently, vitamin D derivatives are used in combination with betamethasone for mild plaque-type psoriasis cases. Moreover, topical calcineurininhibitors (TCIs) and Vitamin D analogues are the treatment of choice among the various topical agents available for different subtypes of psoriasis. For example, TCIs can be used as steroid-sparing agents on the face and intertriginous areas in inverse psoriasis [65]. Tazarotene can be used as an effective maintenance therapy (Table 1). New vehicle formulations, such as gels, lotions, solutions, shampoos, foams, etc., have been developed to improve physicochemical properties, such as lack of adherence, penetration rates, or different pharmacological forms, depending on the application site, thus improving the patient compliance, which is of utmost importance for optimum results. Target-based topical agents are being developed and tested. Moreover, advancement in nanotechnology has led to the possibility of improving the efficacy of topical agents through targeting, improving adherence of pharmaceutical dosage forms and/or drug penetration rates, and minimizing side effects. The formulation of newer molecules and newer drug delivery systems will significantly expand the therapeutic stock for the treatment of psoriasis. As long as there is a general consensus about using topical therapy for mild to moderate psoriasis, there are not a great number of studies about the long-term use of these medicines. There is a wide range of treatments for severe psoriasis, from topical gels to systemic oral drugs. There are some different types, with different targets, having a wide range of effectiveness and safety.