Quercetin and omega-3 fatty acids-loaded lipid hybrid nanoassemblies as promising antimicrobial biofilm strategies

Biofilm formation is usually associated with antimicrobial treatment failure and the development of chronic infections. Therefore, it is important to develop new strategies to address wounds treatment. Nanocarriers can be engineered with precision, tailored to target specific bacterial strains, or disrupt biofilm architecture. This work aimed to evaluate the potential of quercetin (Q) and/or omega-3 fatty acids (ω 3 )-loaded in hybrid nanoassemblies composed by nanostructured lipid carriers (NLCs) and nanofibers as an innovative strategy to prevent biofilm formation on wounds. NLCs were homogeneous in terms of size and charge, with mean hydrodynamic diameter less than 200 nm and a negative charge. The antibiofilm activity of Q and ω 3 , both free and loaded on NLCs, on S. aureus and E. coli biofilms, was analysed. NLCs have an inhibitory effect, especially those containing ω 3 . The encapsulated compounds also demonstrated increased antibiofilm activity compared to free compounds. Q and/or ω 3 , free or loaded in NLCs, showed no cytotoxicity on cell-cultured fibroblasts. After 7 days, NLCs, especially those containing ω 3 , had a positive effect on cell proliferation, potentially aiding in tissue regeneration. NLC-enriched nanofibers with a porous structure allow for exchange of exudates, gases, and nutrients, while their random orientation mimics the skin's extracellular matrix, aiding cell adhesion and proliferation. The nanofibers present good mechanical strength and an increased surface area that enhances diffusion, enabling rapid and complete Q release, which is beneficial for anti-biofilm activity. Q and ω 3 -loaded NLCs enriched nanofibers may be a promising antibiofilm treatment strategy, allowing for proper delivery of these agents with antimicrobial activity while preventing biofilm formation on wounds. • Q and/or ꞷ 3 -loaded NLCs significantly inhibit S. aureus and E. coli biofilms • Q and/or ꞷ 3 -loaded NLCs promote fibroblast proliferation • NLCs-enriched nanofibers showed adequate mechanical/physical properties • The obtained rapid and complete Q release is critical for anti-biofilm activity.