Revolutionizing Psoriasis Topical Treatment: Enhanced Efficacy Through Ceramide/Phospholipid Composite Cerosomes Co-Delivery of Cyclosporine and Dithranol: In-Vitro, Ex-Vivo, and in-Vivo Studies

Abstract

Purpose Improving the treatment of psoriasis is a serious challenge today. Psoriasis is an immune-mediated skin condition affecting 125 million people worldwide. It is commonly treated with cyclosporine-A (CsA) and dithranol (DTH). CsA suppresses the activation of T-cells, immune cells involved in forming psoriatic lesions. Meanwhile, DTH is a potent anti-inflammatory and anti-proliferative drug that effectively reduces the severity of psoriasis symptoms such as redness, scaling, and skin thickness. CsA and DTH belong to BCS class II with limited oral bioavailability. We aim to develop a drug delivery system for topical co-delivery of CsA and DTH, exploring its therapeutic potential. Methods Firstly, we developed a niosomal drug delivery system based on ceramide IIIB to form Cerosomes. Cerosomes were prepared from a mixture of Ceramide, hyaluronic acid, and edge activator using a thin-film hydration technique. To co-deliver CsA and DTH topically for the treatment of psoriasis. These two hydrophobic drugs encapsulated into our synthesized positively charged particle cerosomes. Results Cerosomes had an average particle size of (222.36 nm± 0.36), polydispersity index of (0.415±0.04), Entrapment Efficiency of (96.91%± 0.56), and zeta potential of (29.36±0.38mV) for selected formula. In vitro, In silico, in vivo, permeation, and histopathology experiments have shown that cerosomes enhanced the skin penetration of both hydrophobic drugs by 66.7% compared to the CsA/DTH solution. Imiquimod (IMQ) induced psoriatic mice model was topically treated with our CsA/DTH cerosomes. We found that our formulation enhances the skin penetration of both drugs and reduces psoriasis area and severity index (PASI score) by 2.73 times and 42.85%, respectively, compared to the CsA/DTH solution. Moreover, it reduces the levels of proinflammatory cytokines, TNF-α, IL-10, and IL-6 compared to CsA/DTH solution administration. Conclusion The Cerosomes nano-vesicle-containing CsA/DTH represents a more promising topical treatment for psoriasis, giving new hope to individuals with psoriasis, compared to commercial and other conventional alternatives.

Green Synthesis of Zinc Oxide Nanoparticles from Althaea officinalis Flower Extract Coated with Chitosan for Potential Healing Effects on Diabetic Wounds by Inhibiting TNF-α and IL-6/IL-1β Signaling Pathways

“…The reduction in LPS-induced wound inflammation, either by promoting IL-10 or inhibiting IL-6, TNF-α, and IL-1β, has been highlighted by previous studies. 44 Our investigation revealed that AO-ZnO-NPs-chitosan gel treatment resulted in a significant decrease in serum levels of IL-6, TNF-α, and IL-1β, along with an increase in IL-10 levels three hours after LPS injection, when compared to Althaea Officinalis extract. Therefore, we propose that the modulation of immunoregulatory cytokines is how AO-ZnO-NPs-chitosan gel achieves enhanced therapeutic benefits in wound healing.…”

“…Furthermore, when applied to cells, the AO-ZnO-NPs-chitosan gel exhibited a significant increase in flow, particularly in response to stimuli like acute inflammation or oxidative stress. 44 This suggests that the gel formulation may provide a sustained release of proteins, thereby enhancing their bioavailability even in compromised skin conditions. Given that the components of the formulation are generally considered safe, these findings support the biocompatibility of the AO-ZnO-NPs-chitosan gel when in contact with skin cells.…”

“… 24 Additionally, the synthesis of zinc oxide nanoparticles (ZnO) has anti-inflammatory, antimicrobial, and wound-healing properties. 44 When combined with CS gel, A.O . aqueous extract, and ZnO exhibited significantly better wound healing.…”

Recent Advancements and Trends of Topical Drug Delivery Systems in Psoriasis: A Review and Bibliometric Analysis

“… [ 66 ] Ceramide, hyaluronic acid, edge activator 222.36 ± 0.36 nm Thin film hydration method Cyclosporine-A, dithranol C57BL/6 mice Cyclosporine-A and dithranol, which have limited oral bioavailability, were encapsulated in ceramide/phospholipid composite cerosomes to enhance skin penetration and exert antiproliferative effects. [ 67 ] 7 Emulsion Drug Delivery Systems Fish oil, linseed oil, tween 80, transcutol-P <130 nm Spontaneous emulsification method, high pressure homogenization technique Tacrolimus Albino mice The intervention enhances medication efficacy by minimizing irritation and promoting greater patient compliance. [ 68 ] Span 80, tween 80 16.46 ± 0.07 nm - Tacrolimus SD rats, BALB/c mice It enhances medication solubility and permeability, acting as an adjuvant in anti-psoriasis treatment.…”

“…Compared to a CsA/DTH solution, the cerosomes enhanced drug penetration by 66.7% and decreased PASI by 2.73-fold and 42.85%, respectively. 67 …”