{"title":"Aerosolizable Pyrazinamide-Loaded Biodegradable Nanoparticles for the Management of Pulmonary Tuberculosis.","authors":"Komal Parmar, Swati Sondarva","doi":"10.1089/jamp.2022.0078","DOIUrl":null,"url":null,"abstract":"<p><p><b><i>Background:</i></b> Pyrazinamide is a Biopharmaceutical Classification System class III antibiotic indicated for active tuberculosis. <b><i>Methods:</i></b> In the present work, pyrazinamide-loaded biodegradable polymeric nanoparticles (PNPs) based dry powder inhaler were developed using the double emulsion solvent evaporation technique and optimized using design of experiments to provide direct pulmonary administration with minimal side effects. Batches were characterized for various physicochemical and aerosol performance properties. <b><i>Results:</i></b> Optimized batch exhibited particle size of 284.5 nm, % entrapment efficiency of 71.82%, polydispersibility index of 0.487, zeta potential of -17.23 mV, and <i>in vitro</i> drug release at 4 hours of 79.01%. Spray-dried PNPs were evaluated for drug content, <i>in vitro</i> drug release, and kinetics. The particle mass median aerodynamic diameter was within the alveolar region's range (2.910 μm). In the trachea and lung, there was a 2.5- and 1.2-fold increase in <i>in vivo</i> deposition with respect to pure drug deposition, respectively. <i>In vitro</i> drug uptake findings showed that alveolar macrophages with pyrazinamide PNPs had a considerably higher drug concentration. Furthermore, accelerated stability studies were carried out for the optimized batch. Results indicated no significant change in the evaluation parameters, which showed stability of the formulation for at least a 6-month period. <b><i>Conclusion:</i></b> PNPs prepared using biodegradable polymers exhibited efficient pulmonary drug delivery with decent stability.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"30-40"},"PeriodicalIF":2.0000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/jamp.2022.0078","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/10 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Pyrazinamide is a Biopharmaceutical Classification System class III antibiotic indicated for active tuberculosis. Methods: In the present work, pyrazinamide-loaded biodegradable polymeric nanoparticles (PNPs) based dry powder inhaler were developed using the double emulsion solvent evaporation technique and optimized using design of experiments to provide direct pulmonary administration with minimal side effects. Batches were characterized for various physicochemical and aerosol performance properties. Results: Optimized batch exhibited particle size of 284.5 nm, % entrapment efficiency of 71.82%, polydispersibility index of 0.487, zeta potential of -17.23 mV, and in vitro drug release at 4 hours of 79.01%. Spray-dried PNPs were evaluated for drug content, in vitro drug release, and kinetics. The particle mass median aerodynamic diameter was within the alveolar region's range (2.910 μm). In the trachea and lung, there was a 2.5- and 1.2-fold increase in in vivo deposition with respect to pure drug deposition, respectively. In vitro drug uptake findings showed that alveolar macrophages with pyrazinamide PNPs had a considerably higher drug concentration. Furthermore, accelerated stability studies were carried out for the optimized batch. Results indicated no significant change in the evaluation parameters, which showed stability of the formulation for at least a 6-month period. Conclusion: PNPs prepared using biodegradable polymers exhibited efficient pulmonary drug delivery with decent stability.
期刊介绍:
Journal of Aerosol Medicine and Pulmonary Drug Delivery is the only peer-reviewed journal delivering innovative, authoritative coverage of the health effects of inhaled aerosols and delivery of drugs through the pulmonary system. The Journal is a forum for leading experts, addressing novel topics such as aerosolized chemotherapy, aerosolized vaccines, methods to determine toxicities, and delivery of aerosolized drugs in the intubated patient.
Journal of Aerosol Medicine and Pulmonary Drug Delivery coverage includes:
Pulmonary drug delivery
Airway reactivity and asthma treatment
Inhalation of particles and gases in the respiratory tract
Toxic effects of inhaled agents
Aerosols as tools for studying basic physiologic phenomena.