AbstractHealthcare associated infections (HCAIs) are one of the most global causes of mortality and morbidity. Surgical site infections are a type of HCAI which is most frequently caused by Methicillin resistant Staphylococcus aureus (MRSA). Mupirocin (MUP) is a topical antibiotic with promising potential for eradication of MRSA colonisation, however, most topical antibiotics have limited capability to penetrate the stratum corneum and reach deeper skin. A nanoemulsion (NE) is an advanced drug delivery system with promising potential to enhance the transdermal permeability of topical antibacterial agents. However, its topical application to the skin is not feasible because of its low viscosity, low spreadability and poor retention. Incorporation of the NE into a hydrogel base may help thicken the formulation and improve its rheological behaviour and other physicochemical properties. The aim of this study was to develop MUP NE and nanoemulgels (NEG) in order to study their physicochemical characteristics and the promising potential for topical application.
A NEG of MUP was prepared by incorporating MUP NE into Carbopol hydrogel at a ratio of 1:1. Mupirocin loaded o/w NEs were prepared using high shear homogenisation followed by ultrasonication. Eucalyptus oil or eucalyptol, Tween® 80 and Span® 80 were used as the oil phase (O), surfactant (S) and cosurfactant (CoS) at a ratio of (O:S:CoS, 1.5:1:0.5), respectively. Physicochemical characterisation, thermodynamic analysis, in vitro permeation studies and quantification of drug in skin of both NE and NEG formulations were carried out.
Stable NEs based on both oils were obtained at 25 °C with droplet size < 38 nm and PDI < 0.17 over 3 months. There was no significant difference in skin permeability among NE formulations, while they exhibited better skin permeation than the control, a marketed cream. MUP NE EU exhibited higher MUP deposition into skin after 8 h than other formulations including the control, while MUP NE EO1 showed permeation superiority after 24 h. Stable NEG formulations at 25 °C with higher zeta potential of -20 – -35 mV than corresponding NE were obtained. All NEG formulations exhibited non-Newtonian behaviour with approximately similar spreadability (~ 17 g.mm.s-1). All the developed NEGs were stable at 4, 25 and 40 °C except MUP NEG EO1 which liquified and at 40 °C indicating poorer stability. NEG formulations showed lower skin permeability than NEs, however, the local accumulation efficiency (LAC) of MUP from NEG after 8 h was significantly greater than the control, with no significant difference after 24 h.
These findings highlighted the possibility for the development of NEs based on different essential oils for the acute or prophylactic management of skin infections. In addition, they indicated the promising potential of the NEG formulations for topical delivery of antibacterial drugs particularly when targeting skin lesions requiring high skin deposition and low permeability.
|Date of Award
|28 Sep 2023
|Barbara Conway (Main Supervisor), Muhammad Usman Ghori (Co-Supervisor) & Karen Ousey (Co-Supervisor)