The Impact of Surfactants in Tailoring Nanostructured Lipid Carriers for Inhaled Levofloxacin

Abstract

Nanoparticles can enhance pulmonary delivery of antibiotics by modifying or targeting drug release, increasing drug stability, decreasing mucus entrapment, disrupting biofilms, and reaching the deep lung. Surfactants play a key role as coating agents for several nanoparticle types, modulating interfacial interactions with drugs and the environment. Specifically, levofloxacin (LV) inhalation can benefit from its loading into nanostructured lipid carriers (NLCs) for high drug entrapment, sustained release, and antimicrobial efficacy, but no studies have focused on the relevance of the surfactant type on its biological and physicochemical performance. Therefore, this study aimed to evaluate the impact of three nonionic surfactants─polysorbate 80 (P80), poloxamer 407 (P407), and poloxamer 188 (P188)─on the physicochemical and biological in vitro performance of LV-loaded NLCs. NLCs presented similar physicochemical properties, with average sizes of 100–200 nm, polydispersity <0.3, slightly negative ζ-potential (−5 to −19 mV), high drug entrapment efficiency (>77%), and rounded-shape morphology. The P188 coating tends to have a prolonged release profile compared to the other formulations, but further studies should be conducted to confirm this tendency. All formulations preserved the antimicrobial activity of LV in vitro compared to the free LV against Klebsiella pneumoniae, Staphylococcus aureus, Burkholderia cepacia, and Haemophilus influenzae. Notably, P407 was the only surfactant able to maintain the biofilm inhibition of B. cepacia promoted by LV up to half the minimum inhibitory concentration (MIC) under the tested conditions. This is the first evidence of LV efficacy against biofilms of this species, highlighting the importance of LV application against this undervalued but deadly infection agent in patients with cystic fibrosis. Concerning device compatibility, P407-stabilized NLCs retained their size and PDI within the same range after nebulization through a vibrating mesh, which is favorable for future pulmonary delivery. In summary, these findings highlight the importance of surfactant type selection, indicating the preliminary feasibility of the P407-based formulation and providing a foundation for future investigations on the pulmonary delivery of LV.