Clinical insights into topically applied multipronged nanoparticles in subjects with atopic dermatitis

Combinational therapy of hydrocortisone (HC), a topical steroid with an antioxidant hydroxytyrosol (HT) was used by co-loading into chitosan nanoparticles (CSNPs) for its clinical efficacy and safety against atopic dermatitis (AD). NPs were characterized while the complexation of drugs with CS was investigated by exploiting molecular docking and molecular dynamic (MD) simulations to determine the drug release pattern and stability of NPs in an aqueous medium. A double-blind, randomized controlled study was performed in 9 subjects of mild-moderate AD for six weeks. Subjects were monitored at pre-determined time intervals for transepidermal water loss (TEWL), erythema intensity, melanin level, physical appearance as well as eczema area severity index (EASI) score. An invasive safety study was conducted by analyzing blood samples. The particle size was 267 ± 4 nm. In-silico binding energies showed that CS formed a stronger complex with HC (cScore = 4.21) than HT (cScore = 3.55). Molecular mechanics energies combined with the Poisson–Boltzmann or generalized Born and surface area (MMGB/PBSA) computed binding affinities were also consistent with molecular docking results. Significant improvement in the drugs loaded CSNPs group was observed based on their TEWL, erythema intensity, melanin level, physical appearance and EASI score (>1). These preliminary results demonstrated that CSNPs cream may be viable and superior to the commercial formulation without topical steroid-related problems.