Novel Chitosan Nanoparticles Loaded with Methotrexate for Topical Treatment of Psoriasis

In this work, CS NPs were prepared by the ionic gelation method and encapsulated with MTX to treat psoriasis dermally.A major drawback of using MTX to treat psoriasis is its limited diffusion through the skin, which may cause insufficient penetration of MTX into the basal layer of the epidermis, where psoriatic cells are generated.Nanoparticles have been used to enhance MTX diffusion through the skin. The system prepared in this work is expected to direct the drug to psoriasis cells by enhancing the drug diffusion through the skin, which will increase the amount of the drug reaching the epidermis. This is expected to enhance the effectiveness of the drug and to decrease its systemic side effects.Five formulations of Chitosan nanoparticles were prepared and loaded with Methotrexate using the ionic gelation technique. Particle size, dispersity, charge, loading capacity and encapsulation efficacy were measured. Characterization of prepared nanoparticles was conducted to confirm the formation of CS-NPs, successful encapsulation of MTX and its compatibility with other formulation components. In vitro drug release from CS-NPs, its permeation and accumulation in rats' skin were explored. Finally, the anti-psoriatic activity was assessed using the "mouse tail model."The results showed that the sizes ranged from 132.13 ± 0.70 to 300.60 ± 4.81 nm, where SEM demonstrated the spherical and uniform distribution of the NPs. The surface charge of all NPs was highly positive and ranged from 20.22 ± 1.10 to 30.90 ± 0.70 mV. Further, the EE% and LC% of the nanoparticles were in the range of 77.72%-92.70% and 17.90%-21.81%, respectively. in vitro, the release of methotrexate from the nanoparticles was sustained. Additionally, both the permeation and retention of drugs within the skin were enhanced significantly using this system. Eventually, orthokeratosis% and drug activity% showed significant superiority of MTX-CS NPs over the free drug in treating psoriasis in model mice.In conclusion, MTX-CS NPs can be used to enhance the treatment of psoriasis topically.