Abstract
The entire world has recently been witnessing an unprecedented upsurge in microbial lung infections. The major challenge encountered in treating the same is to ensure the optimum drug availability at the infected site. Aerosolization of antimicrobials, in this regard, has shown immense potential owing to their localized and targeted effect. Efforts, therefore, have been undertaken to systematically develop lung-phosphatidylcholine-based lipid nanovesicles of voriconazole for potential management of the superinfections like aspergillosis. LNVs, prepared by thin-film hydration method, exhibited a globule size of 145.4 ± 19.5 nm, polydispersity index of 0.154 ± 0.104 and entrapment efficiency of 71.4 ± 2.2% with improved in vitro antifungal activity. Aerodynamic studies revealed a microdroplet size of ≤5 μm, thereby unraveling its promise to target the physical barrier of lungs effectively. The surface-active potential of LNVs, demonstrated through Langmuir-Blodgett troughs, indicated their ability to overcome the biochemical pulmonary surfactant monolayer barrier, while the safety and uptake studies on airway-epithelial cells signified their immense potential to permeate the cellular barrier of lungs. The pharmacokinetic studies showed marked improvement in the retention profile of voriconazole in lungs following LNVs nebulization compared to pristine voriconazole. Overall, LNVs proved to be safe and effective delivery systems, delineating their distinct potential to efficiently target the respiratory fungal infections.
Highlights
Of late, the impact of microbial lung infections on the healthcare sector has been overwhelming
Several clinical studies have reported the emergence of Covid-19 associated pulmonary aspergillosis (CAPA), as it is associated with high mortality rates (Alanio et al, 2020; Koehler et al, 2020b; Rutsaert et al, 2020)
Inhalable lipid nanovesicles (LNVs) of voriconazole were prepared as an alternative to the conventional therapeutic regimens employing lung-endogenous phospholipids
Summary
The impact of microbial lung infections on the healthcare sector has been overwhelming. The devastating Covid-19 wave, being witnessed across the world, has further augmented the susceptibility of patients to superinfections like invasive pulmonary aspergillosis (IPA) and mucormycosis (black fungus disease), making the treatment of the deadly coronavirus (SARS-CoV-2) even more complicated (Machado et al, 2021; Marr et al, 2021). The virus, directly targets and disrupts the airway barriers and enables the infiltration of Aspergillus into the lung epithelial cells, thereby causing Covid-19 associated pulmonary aspergillosis (CAPA) (Koehler et al, 2020a; Arastehfar et al, 2020). Several clinical studies have reported the emergence of CAPA, as it is associated with high mortality rates (Alanio et al, 2020; Koehler et al, 2020b; Rutsaert et al, 2020). The first-line treatment regimen includes using azoles, like voriconazole, and other antiviral agents, while liposomal amphotericin B is employed in azole-resistant cases (Koehler et al, 2020a). Researchers worldwide have been working hard to deal with this intricate situation and explore diverse approaches to develop a safe, effective and biocompatible formulation with minimal side effects
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