Oils, including essential oils and their constituents, are widely reported to have penetration enhancement activity and have been incorporated into a wide range of pharmaceutical formulations. This study sought to determine if there is an evidence base for the selection of appropriate oils for particular applications and compare their effectiveness across different formulation types. A systematic review of the data sources, consisting of Google Scholar, EMBASE, PubMed, Medline, and Scopus, was carried out and, following screening and quality assessment, 112 articles were included within the analysis. The research was classified according to the active pharmaceutical ingredient, dosage form, in vitro/in vivo study, carrier material(s), penetration enhancers as essential oils, and other chemical enhancers. The review identified four groups of oils used in the formulation of skin preparations; in order of popularity, these are terpene-type essential oils (63%), fatty acid-containing essential oils (29%) and, finally, 8% of essential oils comprising Vitamin E derivatives and miscellaneous essential oils. It was concluded that terpene essential oils may have benefits over the fatty acid-containing oils, and their incorporation into advanced pharmaceutical formulations such as nanoemulsions, microemulsions, vesicular systems, and transdermal patches makes them an attractive proposition to enhance drug permeation through the skin.

Mupirocin (MUP) is an effective topical antibiotic with poor skin permeability; however, its skin permeability can be improved by a nanoemulsion formulation based on eucalyptus oil or eucalyptol. Despite this improvement, the nanoemulsion has limitations, such as low viscosity, low spreadability, and poor retention on the skin. To overcome these limitations, the aim of this study was to develop a nanoemulgel formulation that would enhance its rheological behaviour and physicochemical properties. The MUP nanoemulgel was prepared by incorporating a preprepared MUP nanoemulsion into Carbopol gel at a concentration of 0.75% in a 1:1 ratio. The nanoemulgel formulations were characterised and evaluated for their physicochemical and mechanical strength properties, rheological behaviour, and in vitro skin permeation and deposition, as well as antibacterial studies. Both nanoemulgels exhibited stability at temperatures of 4 and 25 °C for a period of 3 months. They had a smooth, homogenous, and consistent appearance and displayed non-Newtonian pseudoplastic behaviour, with differences in their viscosity and spreadability. However, both nanoemulgels exhibited lower skin permeability compared to the marketed control. The local accumulation efficiency of MUP from nanoemulgel after 8 h was significantly higher than that of the control, although there was no significant difference after 24 h. Micro-CT scan imaging allowed visualisation of these findings and interpretation of the deposited drug spots within the layers of treated skin. While there were no significant differences in the antibacterial activities between the nanoemulgels and the control, the nanoemulgels demonstrated superiority over the control due to their lower content of MUP. These findings support the potential use of the nanoemulgel for targeting skin lesions where high skin deposition and low permeability are required, such as in the case of topical antibacterial agents.

Mupirocin (MUP) is a topical antibacterial agent used to treat superficial skin infections but has limited application due to in vivo inactivation and plasma protein binding. A nanoemulsion formulation has the potential to enhance the delivery of mupirocin into the skin. MUP-loaded nanoemulsions were prepared using eucalyptus oil (EO) or eucalyptol (EU), Tween^® 80 (T80) and Span^® 80 (S80) as oil phase (O), surfactant (S) and cosurfactant (CoS). The nanoemulsions were characterised and their potential to enhance delivery was assessed using an in vitro skin model. Optimised nanoemulsion formulations were prepared based on EO (MUP-NE EO) and EU (MUP-NE EU) separately. MUP-NE EO had a smaller size with mean droplet diameter of 35.89 ± 0.68 nm and narrower particle size index (PDI) 0.10 ± 0.02 nm compared to MUP-NE EU. Both nanoemulsion formulations were stable at 25 °C for three months with the ability to enhance the transdermal permeation of MUP as compared to the control, Bactroban^® cream. Inclusion of EU led to a two-fold increase in permeation of MUP compared to the control, while EO increased the percentage by 48% compared to the control. Additionally, more MUP was detected in the skin after 8 h following MUP-NE EU application, although MUP deposition from MUP-NE EO was higher after 24 h. It may be possible, through choice of essential oil to design nanoformulations for both acute and prophylactic management of topical infections.

Highlights• Coaxial nanofibers enabled controlled transdermal nicotinamide delivery.• PEO molecular weight controlled fiber morphology, mechanical, and hydration behaviour.• Surface roughness and OCT attenuation increased with increasing PEO molecular weight.• UV imaging provided real-time visualisation of drug permeation using a 3D-printed diffusion cell.