Yumin Li,Lianghao Huang,Sifeng Zhu,Xiaoyao Ma,Zimin Cai,Zhao Yang,Cheng Wang,Wei Wang
Influenza A viruses (IAVs) necessitate urgently development of novel treatment approaches due to their high variability and widespread drug resistance. Penindolone (PND), distinct from anti-IAVs drugs on the market, is a promising IAVs inhibitor specifically targeting both HA1 and HA2 subunits of virus hemagglutinin. However, its clinical utility is hindered by poor water solubility and inadequate oral bioavailability. This study was for the first time to propose a practical and potent delivery approach for PND against IAVs. Inhalable PND-loaded nanoparticles (PND-NPs) were obtained through hydrophobic interactions of PND and monomethoxy poly(ethylene glycol)-poly(D, l -lactide) copolymer, realizing efficient loading of PND. The in vitro experiments demonstrated that PND-NPs exhibited lower cytotoxicity and more potent antiviral activity against IAVs than free PND (IC 50 2.5 μM vs. 42.9 μM for A/Virginia/ATCC1/2009 and 11 μM vs. 73 μM for A/Puerto Rico/8/3 (PR/8)), thus expanding the therapeutic window. In the PR/8 infected mice model, the local delivery of PND-NPs via aerosolized inhalation demonstrated that PND-NPs, superior to the effects of the clinical drug oseltamivir, effectively reduced viral load and pro-inflammatory cytokines in the lungs, and significantly prolonged the survival time of mice (twice as long as the oseltamivir treatment group). Overall, non-invasive inhalation therapy with PND-NPs holds significant promise for clinical application in the antiviral domain.
Difeng Zhu,Jing Dou,Li Ping,Yawen Hong,Chao Chen,Chenxing Yuan,Qixiu Li,Wenjie Luo,Xiaoqing Chi
Aerosol inhalation therapy offers significant benefits in treating chronic obstructive pulmonary disease, including rapid onset of action and reduced systemic side effects. Revefenacin, a long-acting bronchodilator, has demonstrated efficacy in improving lung function and alleviating chronic obstructive pulmonary disease symptoms through aerosol delivery. However, quantitative methods for determining the inhaled concentration of revefenacin aerosol remain limited. This study developed and validated a rapid, robust ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to quantify revefenacin aerosol concentration. The method, with an analysis time of 2 min, exhibited excellent specificity, precision, and a lower limit of quantification of 2 ng/mL. The aerosol extraction recovery averaged 98.5%. The method was successfully applied to assess aerosol concentration and aerodynamic particle size distribution under different sampling conditions. Results showed that after 15 min of nebulization, the average aerosol concentrations collected using syringe aspiration and impactor sampling methods were 0.98 and 0.95 mg/m 3 , respectively, demonstrating consistency between the techniques. Aerodynamic particle size distribution analysis revealed stable particle size distribution with atomization times of 5 and 15 min, yielding mass median aerodynamic diameters of 2.31 and 2.35 µm, fine particle fractions of 76.5% and 76.7%, and geometric standard deviations of 2.44 and 2.41, respectively. These findings indicate that the aerodynamic properties of revefenacin aerosol remain stable over prolonged nebulization. This study establishes a reliable analytical method for revefenacin aerosol quantification and provides valuable insights into its aerodynamic characteristics, supporting its further application in chronic obstructive pulmonary disease treatment.
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