期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 12, 期 7, 页码 4414-4434出版社
MDPI
DOI: 10.3390/ijms12074414
关键词
tuberculosis; drug delivery; immune response; liposomes
资金
- National Research Council of Thailand
- NANOTEC center of Excellence at Prince of Songkla University, Thailand
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. m, with fine particle fractions (aerosolized particles less than 4.4 mu m) 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-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), 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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