Solvent-free green preparation of niacinamide niosomes for targeting UVB-induced hyperpigmentation: QbD-based optimisation and in vivo assessment

Hyperpigmentation is often driven by ultraviolet (UV)-induced inflammation and melanogenesis. This study aimed to develop a novel, eco-friendly niacinamide (NIA) nano-delivery system to overcome the skin barrier and effectively target both inflammation and pigmentation associated with ultraviolet B (UVB) damage. Employing a Quality-by-Design (QbD) approach, we utilised a D-optimal response surface design to fabricate and optimise solvent-free niacinamide niosomes (NIA-NIs). Particle size (PS) was minimised and zeta potential (ZP) maximised for enhanced stability and skin penetration using novel complete solvent-free ultrasonication method. Morphology was confirmed by transmission electron microscopy (TEM). The therapeutic efficacy of the optimised formulation was validated in a rat-UVB-induced skin-damage model, with outcomes assessed through histopathological examination and inflammatory cytokine quantification. The optimised NIA-NIs exhibited a nano-size of 272 nm ± 9.5 and a high negative charge ZP of −26.9 mV ± 1.2. TEM confirmed spherical morphology and nano-scale size. The niosomal formulation demonstrated profound in vivo superiority in suppressing inflammation, reducing TNF-α and IL-6 levels by 54% and 29%, respectively. Histopathology confirmed near-complete skin architecture restoration, markedly reducing hyperkeratosis, inflammatory infiltration and collagen disruption, effects that were only partial using the free drug. Niosomes significantly enhance NIA’s efficacy through targeted delivery, establishing them as a promising and sustainable nano-therapy for effectively treating hyperpigmentation and photo-damaged skin.