Hybrid Ofloxacin/eugenol co-loaded solid lipid nanoparticles with enhanced and targetable antimicrobial properties

Abstract

In the global context of an imminent emergence of multidrug-resistant microorganisms, the present work combined the use of nanotechnology and the therapeutic benefits of natural compounds as a strategy to potentiateantimicrobial action of the wide-spectrum antibiotic Ofloxacin (Ofx). Hybrid solid lipid nanoparticles (SLN) were synthesized by incorporation of chitosan (Chi, a cationic biopolymer with antimicrobial activity) and eugenol(Eu, a phenolic compound that interferes with bacterial quorum sensing) into a lipid matrix by hot homogenization/ultrasonication method. The developed SLN/Chi/Eu sustainably released the encapsulated Ofx for 24h.Characterization by DLS, TEM, DSC, TGA and XRD revealed the presence of positively charged spherical nanoparticles with diameters around 300nm and Ofx entrapped in amorphous state. The SLN exhibited an enhancedbactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus. The minimum inhibitory concentration (MIC) for free and nanoencapsulated Ofx formulations was below 1.0µg/ml. The MIC values decreased by 6.1- to 16.1-fold when Ofx was encapsulated in SLN/Chi/Eu. Fluorescent-labeled nanoparticles had the ability to interact with the bacterial cell membrane. Selective toxicity of SLN/Chi/Eu-Ofx was tested in the range of 0.3?30.0µg/ml and showed no toxicity up to 3.0µg/ml Ofx in human cell models (A549 and Wi-38) at 24h and 48h exposure. It was proved that the administration of hybrid SLN to mice by dry powder inhalation reached therapeutic Ofx levels in lungs.