title: Isoniazid proliposome powders for inhalation-preparation, characterization and cell culture studies.
abstract: The aims of this study were to develop proliposome powders containing isoniazid (INH) in a dry powder aerosol form. INH-proliposome powders were prepared by a spray drying method. Proliposome physicochemical properties were determined using cascade impactor, X-ray diffraction and differential scanning calorimetry. The toxicity of proliposomes to respiratory-associated cell lines and its potential to provoke immunological responses from alveolar macrophages (AM) were determined. Free INH and INH-proliposome bioactivities were tested in vitro and in AM infected with Mycobacterium bovis (M. bovis). Aerosolization properties of INH-proliposome powders at 60 L/min, the powders showed mass median aerodynamic diameters of 2.99-4.92 μm, with fine particle fractions (aerosolized particles less than 4.4 μm) of 15-35%. Encapsulation of INH was 18-30%. Proliposome formulations containing INH to mannitol ratios of 4:6 and 6:4 exhibited the greatest overlapping peak between the drug and mannitol. INH-proliposomes were evidently nontoxic to respiratory-associated cells, and did not activate AM to produce inflammatory mediators-including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and nitric oxide-at a toxic level. The efficacy of INH-proliposome against AM infected with M. bovis was significantly higher than that of free INH (p < 0.05). INH-proliposomes are potential candidates for an alternative tuberculosis treatment.
authors.affiliation: Drug Delivery System Excellence Center, Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand; E-Mails: wipaporn_oil@yahoo.com (W.R.); nar_tik@hotmail.com (N.C.); ekawat281@gmail.com (E.T.); sirirat.p@psu.ac.th (S.P.).
authors.forename: Wipaporn
authors.initials: W
authors.lastname: Rojanarat
authors.forename: Narumon
authors.initials: N
authors.lastname: Changsan
authors.forename: Ekawat
authors.initials: E
authors.lastname: Tawithong
authors.forename: Sirirat
authors.initials: S
authors.lastname: Pinsuwan
authors.forename: Hak-Kim
authors.initials: HK
authors.lastname: Chan
authors.forename: Teerapol
authors.initials: T
authors.lastname: Srichana
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000737:chemistry; D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007538:Isoniazid / Q000737:chemistry* / Q000494:pharmacology; D008081:Liposomes / Q000737:chemistry*; D008264:Macrophages / Q000166:cytology / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D009163:Mycobacterium bovis / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry; D011208:Powders / Q000737:chemistry*; D051381:Rats
chemical_list: D000336:Aerosols; D000995:Antitubercular Agents; D016207:Cytokines; D008081:Liposomes; D010713:Phosphatidylcholines; D011208:Powders; D009569:Nitric Oxide; D007538:Isoniazid