Development of azithromycin-loaded microemulsions for the treatment of skin infections

In the recent years bacterial skin infections have been considered one of the major healthcare issues due to the growing emergence of antibiotic-resistant strains of Staphylococcus aureus [1]. Topical application of currently approved antibiotics represents the first strategy for the treatment of skin infections. However, the poor drug retention within the skin can lead to an insufficient drug concentration at the action site and consequently multiple and frequent administrations are generally required, thus impairing patient compliance. In this context, the design of new drug delivery systems useful to improve the treatment of skin infections still remains a challenge of growing urgency [2]. Therefore, the aim of this work was to develop microemulsions containing azithromycin (AZT), a broad-spectrum macrolide antibiotic, for advanced treatment of antibiotic-resistant bacterial infections of the skin. AZT solubility in various oils, surfactants and co-surfactants was firstly assessed to select the main components of the microemulsions. Then, microemulsions composed of different amounts of vitamin E acetate, Labrasol®, Transcutol® P and water were prepared and characterized for their pH, viscosity, droplet size, zeta potential, stability over a storage period of 180 days, ability to release the drug and to promote its retention inside porcine skin. Antimicrobial activity and biocompatibility of microemulsions were also evaluated. Microemulsions showed pH values (around 4.5) in the acceptable pH range of the skin and were characterized by different droplet size (97-138 nm) and viscosity (24-36 mPa*s) depending on their composition. Moreover, the selected microemulsions showed negative zeta potential values (from -22 to -28 mV) which contributed to microemulsion stability over the storage period. Interestingly, all the developed microemulsions provided a prolonged release of AZT, useful to achieve a suitable local drug concentration over the time. Furthermore, microemulsions promoted drug accumulation inside the skin with respect to the control, as consequence of their droplet size, superficial charge and composition. Particularly, microemulsion M1 (vitamin E acetate, Labrasol®, Transcutol® and water 7.7:40.1:18.7:33.5 w/w/w) allowed the retention of a high percentage of drug (46.69 ± 7.96 %) inside the porcine skin, was not cytotoxic and maintained AZT efficacy on S. aureus methicillin-resistant strains. Hence, the developed AZT-loaded microemulsion could be considered a promising tool for topical treatment of skin infections.