Quality-by-design-steered development of nanoemulsion-enabled dissolving microneedle patch for enhanced berberine...

Berberine (BBR) has strong antibacterial, anti-inflammatory, and wound healing effects; its efficacy is limited by poor bioavailability and low skin permeability. In this study, a nano-dressing was developed by incorporating BBR-loaded nanoemulsion (BBR-NE) into a dissolvable microneedle patch to enhance drug delivery to the wound site. The BBR-NE was formulated via the aqueous titration method and optimized using the Box-Behnken design. The optimized formulation exhibited a globule size of 97.89 ± 0.4 nm, PDI 0.277 ± 0.035, and zeta potential of -30.99 ± 0.84 mV. In vitro drug release showed a biphasic pattern, with more than 75% drug released within 24 h, while ex vivo skin permeation demonstrated nearly twofold higher skin penetration compared to suspension, which was further confirmed by CLSM analysis. Additionally, the formulation also showed enhanced antibacterial activity against both Gram-positive and Gram-negative bacteria. The optimized formulation was further incorporated into a dissolvable microneedle patch (Opt-BBR-NE-MN) via a micro-molding technique. The in-vivo evaluation demonstrated that Opt-BBR-NE-MN was non-irritant and significantly accelerated healing in STZ-induced diabetic Wistar rats compared to the control groups. This nanodressing strategy overcomes delivery barriers and improves therapeutic outcomes in chronic wound care, underscoring its clinical potential.