Thermo‐Responsive Microemulsions Containing Deep Eutectic‐Based Antibiotic Formulations for Improved Treatment of Resistant Bacterial Ocular Infections

Abstract

The rise of antibiotic resistant strains, as methicillin-resistant Staphylococcus aureus (MRSA), challenges the current treatment of infections. In the case of ocular infections, antibiotic eye drops are commonly prescribed. However, their efficacy is usually compromised by the low viscosity of these formulations and the eye drainage. To overcome these drawbacks, deep eutectic solvent (DES)-based microemulsions with thermo-responsive character, that increase their viscosity upon contact with the eye have been developed. Using betaine-based DES aqueous solutions, it is possible to increase up to 140-fold the water solubility of the antibiotic chloramphenicol, typically used in ocular infections. The DES solutions containing the antibiotic are applied as water phases in water-in-oil-in-water (w/o/w) microemulsions, being stable up to 3 months. Furthermore, a sustained-release and a higher permeation of the antibiotic through the cornea than that of commercialized eye drops is achieved, while presenting comparable cytotoxicity profiles (cell viabilities > 88%). Higher antimicrobial activity and faster action of the antibiotic in case of infection with MRSA is observed compared to the commercialized formulations (7 log 10 of inactivation in 48 h vs 72 h). Overall, these microemulsions comprising DES are a promising strategy to achieve higher antibiotic effectiveness in the treatment of resistant bacterial infections.