Development of arsenic nanoparticles: a novel topical therapy for psoriasis enhancing skin deposition and preventing relapse for long-term efficacy in imiquimod-induced rat model.

Arsenic (As), an inorganic metalloid, was used historically for the treatment of psoriasis. Despite its applications, concerns regarding its toxicity and carcinogenic potential prompted its reduced utilization in modern medicine. This study aimed to develop two novel nanoparticles for topical treatment of psoriasis: arsenic nanoparticles (AsNPs) and chitosan-coated arsenic nanoparticles (Chi-AsNPs). These formulations were prepared by wet chemical method and designed to leverage As therapeutic effects in psoriasis especially its ability to accumulate in skin tissues, while using chitosan to provide anti-inflammatory benefits and improve skin penetration. AsNPs and Chi-AsNPs showed size of 57.50 ± 5.11 and 81.20 ± 3.21 nm, respectively. The zeta-potential changed from -38 mV (AsNPs) to +45 mV (Chi-AsNPs) which confirms the surface coating. In a rat model with imiquimod-induced psoriasis-lesions, gels containing AsNPs and Chi-AsNPs were compared to gels containing arsenic trioxide (ATO) and a blank chitosan gel. Rats topically treated with AsNPs and Chi-AsNPs gels showed marked improvement in skin appearance, a significant reduction in psoriasis area severity index, and better histological outcomes including reduced epidermal thickening, acanthosis, and hyperkeratosis. Additionally, the expression of the proliferation marker Ki67 in these groups was nearly normal, similar to negative controls. The potential for psoriasis recurrence was assessed and only AsNPs gel effectively inhibited the recurrence of psoriatic lesions. This effect is attributed to the high level of As deposition in the skin from the AsNPs as detected by inductively coupled plasma mass spectrometry. This suggests that AsNPs can act as a reservoir, maintaining therapeutic levels of As in the skin to prevent plaque recurrence even after psoriasis is re-induced.