Multicomponent Lipid Nanoparticles as a Tool to Potentially Improve the Antibiofilm Activity of Resveratrol against MDR Gram-Positive and Gram-Negative Clinical Isolates

Background: Among natural compounds suggested as antimicrobials to overcome the increasing phenomenon of multidrug resistance (MDR), resveratrol (3,5,4 '-trihydroxystilbene; RSV), a phytoalexin commonly found in food and drinks, can be considered a valid alternative. Despite its potentially useful antimicrobial action, orally administered RSV fails in efficacy due to several drawbacks (e.g., first pass effect metabolism, instability, poor water solubility), whereas targeted administration could potentially allow efficacious RSV concentrations against infectious diseases. Additionally, RSV clinical use today is restricted due to low stability and solubility, issues that can be overcome by embedding RSV into lipid-based nanocarriers. Recently, ad hoc designed multicomponent lipid nanoparticles loaded with RSV (mLNP-RSV) were optimized and characterized, showing promising preliminary antibiofilm properties. Methods: In this work, the mLNP-RSV was deeply investigated to assess its potential use for the therapy of Gram-positive and Gram-negative MDR infections. Their antibiofilm action against ATCC 12972 Staphylococcus aureus and ATCC 27853 Pseudomonas aeruginosa strains was examined in terms of inhibition of biofilm production. Then, the assay was conducted again against clinical strains of P. aeruginosa and S. aureus isolated from blood samples of hospitalized patients. Results: The administration of free RSV 16 mu g/mL determined a biofilm production inhibition of 35.6% and 62.1% for ATCC 12972 S. aureus and ATCC 27853 P. aeruginosa, respectively, which was further enhanced by administering an equal RSV dose through mLNP-RSV: 51.4% and 63.0% for S. aureus and P. aeruginosa, respectively. The performed statistical analyses of the data collected from the clinical isolates confirmed the ability of the mLNP-RSV to strongly reduce the formation of a biofilm, especially in P. aeruginosa strains. Conclusions: These findings suggest the potential of the proposed nanosystem to address RSV limitations while supporting its therapeutic action, indicating that mLNP-RSV could serve as a promising tool for the treatment of MDR infections.