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Pulmonary Delivery of Isoniazid in Nanogel-Loaded Chitosan Hybrid Microparticles for Inhalation.
Journal of Aerosol Medicine and Pulmonary Drug Delivery 2018 December 9
PURPOSE: Inhalable pulmonary delivery of isoniazid (INH) may improve the efficacy and reduce drug-resistant problem.
METHOD: INH-loaded chitosan microparticles (Cs-Mps-1-3) were prepared as inhalable carrier for the previously prepared INH-loaded polyvinylpyrrolidone/polyitaconic acid nanoparticles (NPs) using spray-drying technique. Here, Cs-Mps-1-3 are composed of Cs: INH-loaded NPs: Free INH at w/w ratios (1:1:0), (1: 0:1), and (1:1:1), respectively. Subsequently, the prepared Cs-Mps-1-3 characterizations were studied.
RESULTS: Cs-Mps-1-3 showed spherical, smooth, positively charged surface (ζ-potential values +20.2, +28.7, and +22.6) and size range 1.52-3.12 μm. Moreover, Carr's compressibility indices of Cs-Mps-1-3 were 32.5%, 24.8%, and 28.02%, respectively. The In vitro INH released showed good correlation with first-order pattern; with the predominance of diffusion-controlled mechanism. In vitro aerodynamic deposition of Cs-MPs-3 possesses 56.81% effective fine particle fraction with lower impaction loss and device retention (10.47% and 30.9% at mouth and throat and at stage 1), respectively. The minimum inhibitory concentration of Cs-Mps-3 displayed 63-fold more inhibition effects on Mycobacterium tuberculosis than INH solution; owing to the combined effect of positively charged Cs-Mps with their facilitating bacterial cell surface binding and cellular penetration activity of NPs.
CONCLUSION: The promising potential of Cs-Mps-3 as inhalable carrier for pulmonary delivery of INH was recommended.
METHOD: INH-loaded chitosan microparticles (Cs-Mps-1-3) were prepared as inhalable carrier for the previously prepared INH-loaded polyvinylpyrrolidone/polyitaconic acid nanoparticles (NPs) using spray-drying technique. Here, Cs-Mps-1-3 are composed of Cs: INH-loaded NPs: Free INH at w/w ratios (1:1:0), (1: 0:1), and (1:1:1), respectively. Subsequently, the prepared Cs-Mps-1-3 characterizations were studied.
RESULTS: Cs-Mps-1-3 showed spherical, smooth, positively charged surface (ζ-potential values +20.2, +28.7, and +22.6) and size range 1.52-3.12 μm. Moreover, Carr's compressibility indices of Cs-Mps-1-3 were 32.5%, 24.8%, and 28.02%, respectively. The In vitro INH released showed good correlation with first-order pattern; with the predominance of diffusion-controlled mechanism. In vitro aerodynamic deposition of Cs-MPs-3 possesses 56.81% effective fine particle fraction with lower impaction loss and device retention (10.47% and 30.9% at mouth and throat and at stage 1), respectively. The minimum inhibitory concentration of Cs-Mps-3 displayed 63-fold more inhibition effects on Mycobacterium tuberculosis than INH solution; owing to the combined effect of positively charged Cs-Mps with their facilitating bacterial cell surface binding and cellular penetration activity of NPs.
CONCLUSION: The promising potential of Cs-Mps-3 as inhalable carrier for pulmonary delivery of INH was recommended.
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