Nebulizable archaeolipid nanovesicles for drug delivery to the lungs

Abstract

To improve safety and efficacy in the treatment of lungdiseases like asthma and lung infection, medications areroutinely inhaled rather than administered systemically.Inhaled medication can achieve the same effectiveconcentration in lungs at doses lower than by oral orintravenous routes. Moreover, the efficacy of inhaledmedication can be enhanced by performing targeted deliveryto selected body sites, with tailored nanoparticulate carriers.Inhaled nanoparticles preferentially accumulate in lungs, thuslimiting drugs penetration into the bloodstream, consequentlydecreasing adverse systemic side effects. Inhalednanoparticulate medication, however, needs to overcomesome critical drawbacks. Firstly, nanoparticles must towithstand the physical stress produced by the nebulizerforces, and to surpass the barriers imposed by the lungmorphology. Secondly, nanoparticles must avoid the trappinginto the mucociliar escalator, being free to cross thesurfactant layer covering the alveolar epithelium. Thirdly,safety issues related with lung epithelium integrity must beevaluated. This presentation will describe the performance ofnebulizable nanovesicles, as delivery systems for antibiotics oranti-inflammatory drugs to the lungs, on in vitro models ofmucus and surfactant layers and of inflamed alveolarepithelium in an air-liquid interface. The advantages of thesenovel nebulizable nanovesicles made of archaeolipidsextracted from the cellular membrane of archaebacterias willbe analyzed in comparison with conventional inhaledliposomes.