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Isoniazid Proliposome Powders for Inhalation—Preparation, Characterization and Cell Culture Studies
Drug Delivery System Excellence Center, Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand
Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia
* Author to whom correspondence should be addressed.
Received: 19 May 2011; in revised form: 30 June 2011 / Accepted: 30 June 2011 / Published: 7 July 2011
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 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.
Keywords: tuberculosis; drug delivery; immune response; liposomes
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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.
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.
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.