Cutaneous delivery of bioactive components from a rice bran oil nanoemulsion and their biodistribution in porcine and human skin

Rice bran oil (RBO) is rich in antioxidants but the high lipophilicity and low concentration of key active components complicate its formulation for topical delivery. The objective of this study was to develop and to optimize an RBO-based nanoemulsion (RBO-NE) and to investigate the cutaneous delivery of three major bioactive components: 24-methylene cycloartanyl ferulate (24-MCF), γ-tocotrienol, and β-sitosterol. A validated UHPLC-MS/MS method with an internal standard was used to quantify the three molecules. The RBO-NE composition (10% RBO, 5% surfactant mix, 85% ultrapure water) was selected using a pseudo-ternary phase diagram, and ultrasonication was used to produce small globules (222 ± 2 nm, PDI 0.287), which were physically stable for three months at 4 °C. The cutaneous biodistribution of 24-MCF, γ-tocotrienol, and β-sitosterol (after consideration of endogenous β-sitosterol) was determined under infinite and finite dose conditions. Follicular targeting was evaluated by comparing delivery to pilosebaceous unit (PSU)-containing biopsies and control samples. Under infinite dose conditions, RBO-NE increased deposition of the three molecules compared to the control (RBO dispersed in hydroxypropyl-methylcellulose), with preferential accumulation in the epidermis. Delivery to the PSU from RBO-NE was approximately twice that to non-PSU containing skin samples; in contrast, the control showed no difference. Under finite dose conditions, deposition of 24-MCF and γ-tocotrienol in porcine skin was slightly superior to that in human skin. Cutaneous biodistribution studies demonstrated that (i) nanoemulsions could deliver highly lipophilic antioxidants from RBO to the epidermis and dermis, and (ii) the approach enabled simultaneous determination of the penetration profile of multiple RBO components.