Development of a Rosmarinus officinalis extract-loaded nanoemulgel for topical anti-inflammatory delivery: Molecular docking, HPTLC profiling and ex vivo evaluation

Herbal plants like Rosmarinus officinalis exhibit antioxidant and anti-inflammatory properties but face limitations, such as low solubility and poor skin permeability. Nanoemulgels enhance solubility and skin permeation while providing a convenient and patient-friendly topical delivery system. The present investigation aims to develop and evaluate a Rosmarinus officinalis nanoemulgel (RO-NEG) for improved topical delivery and anti-inflammatory activity. The extract yield was 0.85 ± 0.06% and showed strong antioxidant activity with an IC₅₀ of 5.053 ± 0.07 µg/mL, compared to 3.98 ± 0.12 µg/mL for ascorbic acid. HPTLC fingerprinting confirmed rosmarinic acid as a major bioactive constituent with Rf values matching the reference standard. The nanoemulsion was optimized using a Box–Behnken design, yielding a particle size of 138.4 nm, PDI 0.129, and 96% entrapment efficiency, and subsequently incorporated into a nanoemulgel. The optimized RO-NEG exhibited suitable topical properties, including pH 6.2 ± 0.1, viscosity 19,360 ± 350 cP, and spreadability 6.50 ± 0.29 g·cm/s. In vitro release studies showed sustained drug release from RO-NEG (65.20 ± 1.16% at 24 h) compared to the nanoemulsion (80.45 ± 1.17%). Ex vivo skin permeation demonstrated a ∼2.5-fold enhancement in steady-state flux compared to the crude extract. The formulation exhibited significant anti-inflammatory activity through inhibition of protein denaturation and was found to be non-irritant in rabbit skin irritation studies (PII = 0.00). Overall, RO-NEG represents a safe and effective nano-enabled topical system for the treatment of inflammatory conditions. RO-NEG demonstrated improved solubility, skin permeation and sustained drug release along with notable COX inhibition and suppression of protein denaturation suggesting its potential as a naturally derived topical anti-inflammatory formulation.