Abstract
Currently, problems related to antibiotic resistance are shifting the focus of pharmaceutical research towards natural molecules with antibacterial properties. Among them, flavonoids represent promising molecules with strong antibacterial features; however, they have poor biopharmaceutical properties. In this study, we developed solid lipid nanoparticles (SLNs) loaded with the flavanone naringenin (NRG) to offer an option for treating bacterial infections. NRG-SLNs systems were prepared by a solvent emulsification/diffusion and ultrasonication method, using Compritol(®) 888 ATO (COM) as the lipid. The optimal formulation was obtained using a 10% (w/w) theoretical amount of NRG (NRG(10)-SLNs), exhibiting homogeneous sizes (approximately 50 nm and 0.15 polydispersity index), negative zeta potential (-30 mV), and excellent encapsulation parameters (an encapsulation efficiency percentage of 97.9% and a drug content of 4%). NRG(10)-SLNs presented good physical stability over 4 weeks. A cumulative drug release of 55% in 24 h and the prolonged release of the remaining amount over 10 days was observed. In addition, µ-Raman spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and X-ray diffraction measurements were carried out to characterize the drug-lipid interactions. Finally, the in vitro antibacterial and antibiofilm activities of NRG(10)-SLNs were assayed and compared to free NRG. NRG(10)-SLNs were bacteriostatic against Staphylococcus aureus, including the methicillin-resistant S. aureus (MRSA) and Escherichia coli strains. An improvement in the antibacterial activity of NRG-loaded SLNs compared to the free molecule was observed against S. aureus strains, probably due to the interaction of the surfactant-coated SLNs with the bacterial surface. A similar trend was observed for the biofilm inhibition.