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

RODENAK-KLADNIEW B; SCIOLI, S; SBARAGLINI ML; DI IANNI M; RUIZ ME; TALEVI A; ALVAREZ VA; DURAN N; CASTRO G; ISLAN, GA

INTERNATIONAL JOURNAL OF PHARMACEUTICS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2019

0378-5173

In the global context of an imminent emergence of multi-drugresistant microorganisms, the present work combined the use ofnanotechnology and the therapeutic benefits of natural compounds asstrategy to potentiate antimicrobial action of the wide-spectrumantibiotic Ofloxacin (Ofx). Hybrid solid lipid nanoparticles (SLN) weresynthetized by incorporation of chitosan (Chi, a cationic biopolymer withantimicrobial activity) and eugenol (Eu, a phenolic compound thatinterferes with bacterial Quorum Sensing) into a lipid matrix by hothomogenization/ultrasonication method. The developed SLN/Chi/Eusustainably released the encapsulated Ofx for 24 h. Characterization byDLS, TEM, DSC, TGA and XRD revealed the presence of positive chargedspherical nanoparticles with diameters around 300 nm and Ofx entrapped inamorphous state. The SLN exhibited an enhanced bactericidal activityagainst Pseudomonas aeruginosa and Staphylococcus aureus. Minimuminhibitory concentration (MIC) for free and nanoencapsulated Ofxformulations were below 1.0 µg/ml. Reduction of 6.1- to 16.1-folds in theMIC values was observed when Ofx was encapsulated in SLN/Chi/Eu.Fluorescent labeled nanoparticles had the ability to interact withbacterial cell membrane. Selective toxicity of SLN/Chi/Eu-Ofx was testedin the range of 0.3-30.0 µg/ml and showed no toxicity up to 3.0 µg/ml Ofxin human cell models (A549 and Wi-38) at 24 h and 48 h expositionAdministration of hybrid SLN to mice by dry powder inhalation proved toreach therapeutic Ofx levels in lungs.