Janus double-sided nanofibrous patch with asymmetric wettability and controlled topical delivery of tryptanthrin and indirubin as an effective therapy for psoriasis

Local side effects, such as skin dryness and irritation, present significant challenges for topical therapies for psoriasis. There is an urgent need for innovative and safer topical treatments, especially for individuals with mild to moderate psoriasis. In this study, we developed a double-sided Janus-structured nanofibrous patch characterized by asymmetric wettability, with the inner hydrophilic layer topped with a hydrophobic outer polycaprolactone (PCL) layer. The hydrophobic PCL layer functions to facilitate directional hydration through controlled water transport, while the hydrophilic inner layer containing two anti-psoriatic compounds, indirubin and tryptanthrin, ensures optimal anti-psoriasis efficacy. By coaxial electrospinning, the core of the hydrophilic layer contains hyaluronic acid (HA), polyethylene oxide (PEO) and indirubin, while the shell is composed of PCL, PEO, and tryptanthrin. Investigations into the release of anti-psoriatic compounds indicated that both indirubin and tryptanthrin were liberated in bursts. <i>In vitro</i> assessments using psoriatic skin from mice demonstrated notable skin retention and permeation of both compounds within the first 30 min following topical application. Further biological analyses confirmed favorable <i>in vitro</i> biocompatibility, supporting the anticipated therapeutic outcomes, as assessed by severity index scoring and pathological evaluations <i>in vivo</i>. Additionally, an initial human test demonstrated that the efficacy of the double-sided Janus-structured patch was comparable to that of the first-line drug Calcipotriol Ointment during a 4-week topical treatment, with no adverse effects like erythema or pruritus. The unique Janus-structured design effectively combines asymmetric wettability with potent anti-psoriatic ingredients, offering a novel and comprehensive approach to topical therapies for psoriasis.