Therapeutic potential of nanolipoidal α-terpineol in combating keratitis induced by Pseudomonas aeruginosa in the murine model

Abstract

Developing non-antibiotic alternatives is one of the top priorities in healthcare and community settings, especially for combating biofilm-associated infections caused by multi-drug resistant pathogens. The therapeutic efficacy of nanolipoidal α-terpineol was explored against Pseudomonas aeruginosa induced keratitis using the mice model in the present study. Topical administration of nanostructured lipid carriers (NLCs) containing α-terpineol (αT) resulted in significant reduction in bacterial count in corneal tissue by 4 log10 on 5th post infection day. The protective efficacy of αT-NLCs demonstrated improvement in corneal histopathology, decreased the levels of various inflammatory markers including myeloperoxidase (MPO) and reactive nitrogen intermediates (RNI). Further, αT-NLCs treatment showed immunomodulatory effects by manipulating the production of inflammatory cytokines, tumor necrotic factor (TNF-α), macrophage inhibitory protein-2 (MIP-2) and interleukin-2 (IL-2) in infected eyes. In addition, ex vivo studies exhibited enhanced susceptibility of P. aeruginosa towards serum and macrophages in presence of αT-NLCs. A potent antibiofilm effect was also observed by αT-NLCs against P. aeruginosa which was confirmed by fluorescent microscopic analysis. Hence, based on the results of the present study, a novel therapeutic is being proposed for the treatment of biofilm associated keratitis caused by P. aeruginosa.