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Isoniazid Proliposome Powders for Inhalation—Preparation, Characterization and Cell Culture Studies
AbstractThe 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 mm, 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-1b (IL-1b), tumor necrosis factor-a (TNF-a), 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.
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Rojanarat, W.; Changsan, N.; Tawithong, E.; Pinsuwan, S.; Chan, H.-K.; Srichana, T. Isoniazid Proliposome Powders for Inhalation—Preparation, Characterization and Cell Culture Studies. Int. J. Mol. Sci. 2011, 12, 4414-4434.View more citation formats
Rojanarat W, Changsan N, Tawithong E, Pinsuwan S, Chan H-K, Srichana T. Isoniazid Proliposome Powders for Inhalation—Preparation, Characterization and Cell Culture Studies. International Journal of Molecular Sciences. 2011; 12(7):4414-4434.Chicago/Turabian Style
Rojanarat, Wipaporn; Changsan, Narumon; Tawithong, Ekawat; Pinsuwan, Sirirat; Chan, Hak-Kim; Srichana, Teerapol. 2011. "Isoniazid Proliposome Powders for Inhalation—Preparation, Characterization and Cell Culture Studies." Int. J. Mol. Sci. 12, no. 7: 4414-4434.
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