Boosting Gentamicin Activity Against Pseudomonas aeruginosa Using Nano-formulation of Curcumin

Curcumin, a wonder’s natural molecule, has been extensively used for various purposes, including therapeutics. Yet, its water solubility and pH sensitivity are barriers to new therapeutic applications. Nano-formulations of curcumin are a new phase of curcumin prepared to overcome its limitations. Although some of these nano-formulations have also entered the therapeutic domain, however, they have not been well investigated for the reversal of drug resistance especially through efflux pump inhibition. In the present investigation, an attempt has been made to explore a novel and interesting application of synthesized water-soluble nano-formulation of curcumin for its potential as a gentamicin booster in Pseudomonas aeruginosa . Strategic effort to target possible efflux pump inhibition has been given importance. The nano-formulation of curcumin was first prepared by a very simple protocol using a non-ionic surfactant, Tween 80. The water solubility of this nano-formulation was confirmed by zeta potential. The nano-formation and morphology were confirmed by TEM and HR-TEM. An overall spherical-shaped morphology with sizes ranging from 40 to 50 nm was seen in the TEM micrographs. Interestingly, upon HR-TEM analysis, unique nanoflower-like structures were observed. FTIR clearly indicated changes in the functional group of native curcumin. The nano-formulation showed an excellent pH resistance (from pH 3.0 to 9.0) with enhanced free radical scavenging and superoxide scavenging activity. The gentamicin sensitivity enhancement potential of this nano-formulation of curcumin was evaluated for P. aeruginosa which was able to make gentamicin sensitive, where the drug was not able to inhibit alone, whereas water-insoluble curcumin along with gentamicin did not show any inhibition. The presence of efflux pumps are well known in P. aeruginosa , and an increase in drug sensitivity could probably be through efflux pump inhibition which was evidenced using standard verapamil. This study, therefore, highlights the unique concept of making gentamicin sensitive to P. aeruginosa through a new molecular orientation and networking mechanism.