Development of thymoquinone-loaded nanoemulgel using black cumin (Nigella sativa L.) oil and extract for enhanced dermal delivery

Nigella sativa (black seed) is a medicinal plant widely recognized for its antioxidant, anti-inflammatory, and anticancer properties, primarily attributed to its bioactive constituent, thy-moquinone (TQ). However, TQ's poor aqueous solubility and instability limit its therapeutic ef-ficacy in topical applications. This study aimed to develop and characterize a thymoquinone-rich nanoemulgel system using n-hexane-extracted black seed oil and a polyphenol-rich ethanol extract to enhance cutaneous bioavailability and biological performance. Black seed oil was extracted using n-hexane (yield: 31.5%), and the ethanol extract yield-ed 11.25%. Four nanoemulsion formulations (1NP–4NP) were prepared using high-shear ho-mogenization with varying oil, extract, and surfactant ratios. Among them, the dual-loaded formulation 3NP demonstrated superior physicochemical properties, with a droplet size of ~50 nm, low polydispersity index (~0.2), and zeta potential of –25 mV, indicating colloidal stability. FTIR analysis confirmed chemical integrity and successful encapsulation of bioactives without degradation. HPLC and GC-FID quantification revealed that 3NP achieved high (TQ) loading (~240 µg/mL). HPTLC and antioxidant assays (DPPH, CUPRAC) confirmed the presence of multiple antioxidants and their synergistic action. The 3NP nanoemulgel formulated with NaCMC exhibited optimal viscosity, bioadhesion, and spreadability. In vitro release and ex vivo pig skin permeation studies demonstrated signifi-cantly enhanced TQ delivery from 3NP compared to other formulations. MTT cytotoxicity as-says revealed selective toxicity against melanoma cells, with minimal effect on normal fibro-blasts. These findings indicate strong therapeutic potential. In conclusion, the dual-phase Nigel-la sativa nanoemulgel (3NP) represents a promising platform for advanced topical cosmeceuti-cals, warranting further in vivo evaluation and long-term stability testing.