title: Inhaled pyrazinamide proliposome for targeting alveolar macrophages.
abstract: OBJECTIVE
  In this study, pyrazinamide (PZA)-proliposome in a dry powder aerosol form was developed for delivering drugs to alveolar macrophages (AMs) infected with mycobacteria.
  
  
  METHODS
  PZA-proliposomes consisting of pyrazinamide, soybean phosphatidylcholine, cholesterol and porous mannitol were prepared by a spray drying method. The PZA-proliposome physicochemical properties were determined using a cascade impactor, X-ray diffraction, differential scanning calorimetry and infrared spectroscopy. The toxicity of proliposomes to respiratory-associated cell lines (Calu-3, A549 and NR8383) and its potential to provoke immunological responses from AMs were determined. In vivo repeated dose toxicity in rats was evaluated.
  
  
  CONCLUSIONS
  PZA-proliposomes were successfully prepared. For the aerosolization properties of PZA-proliposomes at 60 l/min, the powders showed mass median aerodynamic diameters of 4.26-4.39 µm, with fine particle fractions (aerosolized particles less than 4.4 µm) of 20-30%. Encapsulation of PZA was 26-45%. PZA-proliposomes were less toxic to respiratory-associated cells, and did not activate AMs to produce inflammatory mediators, including interleukin-1β, tumor necrosis factor-α, and nitric oxide, at a toxic level. Renal and liver toxicity in rats were not observed.
  
  
  CONCLUSIONS
  We suggest that PZA-proliposomes are potential candidates for pulmonary tuberculosis treatment.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, Thailand.
authors.forename: Wipaporn
authors.initials: W
authors.lastname: Rojanarat
authors.forename: Titpawan
authors.initials: T
authors.lastname: Nakpheng
authors.forename: Ekawat
authors.initials: E
authors.lastname: Thawithong
authors.forename: Niracha
authors.initials: N
authors.lastname: Yanyium
authors.forename: Teerapol
authors.initials: T
authors.lastname: Srichana
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D002152:Calorimetry, Differential Scanning; D002478:Cells, Cultured; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis; D008081:Liposomes; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D008353:Mannitol / Q000008:administration & dosage; D009569:Nitric Oxide / Q000096:biosynthesis; D010316:Particle Size; D010587:Phagocytosis; D011718:Pyrazinamide / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014961:X-Ray Diffraction
chemical_list: D000336:Aerosols; D053583:Interleukin-1beta; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; D011718:Pyrazinamide; D009569:Nitric Oxide; D008353:Mannitol