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Int. J. Mol. Sci. 2011, 12(7), 4414-4434; doi:10.3390/ijms12074414
Article

Isoniazid Proliposome Powders for Inhalation—Preparation, Characterization and Cell Culture Studies

1
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1
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2
 and
1,*
1 Drug Delivery System Excellence Center, Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand 2 Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia
* Author to whom correspondence should be addressed.
Received: 19 May 2011 / Revised: 30 June 2011 / Accepted: 30 June 2011 / Published: 7 July 2011
(This article belongs to the Section Material Sciences and Nanotechnology)
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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 tuberculosis; drug delivery; immune response; liposomes
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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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.

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