Systematic Review of Lipid Nanoparticle Efficacy for Delivering Antifungal Agents in Invasive Pulmonary Aspergillosis

Abstract

Background: Invasive pulmonary aspergillosis (IPA) remains a lethal infection in immunocompromised hosts, with treatment limited by the poor pharmacokinetics and toxicity of conventional antifungals. Lipid nanoparticles (LNPs) offer a promising delivery platform to overcome these barriers, yet a synthesis of pre-clinical evidence is lacking. Objective: This systematic review aimed to synthesize pre-clinical evidence on the therapeutic potential of LNP-based systems for delivering antifungal agents in the treatment of IPA. Methods: Following PRISMA 2020 guidelines, a comprehensive search of PubMed, Scopus, Web of Science, and Cochrane Library was conducted for studies published from 2014-2024. Included were pre-clinical studies evaluating LNP-encapsulated antifungals in models of IPA, compared to conventional formulations. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment using the SYRCLE tool. Results: Eight studies met the inclusion criteria. All reported that LNP formulations (of amphotericin B, voriconazole, itraconazole, or posaconazole) significantly reduced lung fungal burden and/or improved survival compared to free drug controls (p<0.05). LNPs consistently enhanced drug deposition in lung tissue and, for amphotericin B, demonstrated a reduced nephrotoxic profile. Methodological quality was variable, with frequent unclear risks of bias related to blinding. Conclusion: Pre-clinical evidence robustly indicates that LNP encapsulation enhances the efficacy and safety of antifungal drugs in IPA models. These findings justify accelerated translational research to standardize formulations and advance the most promising candidates toward clinical trials for this high-mortality infection.