Inhalable Particles Containing Rapamycin for Induction of Autophagy in Macrophages Infected with Mycobacterium Tuberculosis
IR@CDRI: CSIR-Central Drug Research Institute, Lucknow
View Archive Info| Field | Value | |
| Creator |
Gupta, Anuradha
Pant, Garima Mitra, Kalyan Madan, Jitender Chourasia, M K Misra, Amit |
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| Date |
2014-06-20T07:07:04Z
2014-06-20T07:07:04Z 2014 |
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| Identifier |
Mol. Pharmaceutics 2014, 11, 1201−1207
http://hdl.handle.net/123456789/1285 |
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| Description |
We investigated whether particles suitable for delivery to alveolar macrophages may provide a means of targeting rapamycin, an inducer of autophagy, to alveolar macrophages as a host-directed anti-tuberculosis agent. Inhalable particles were prepared by spray-drying and characterized using laser scattering and electron microscopy. Their aerodynamic diameter was calculated from bulk and tapped densities. In vitro drug release was studied in PBS containing 1% SDS. In vitro uptake of particles by THP-1 derived macrophages was studied by flow cytometry. Cytotoxicity of the particles towards macrophages and their efficacy against intracellular Mycobacterium tuberculosis were studied using a methyltetrazolium assay and counting bacterial colonies obtained when cell lysates were plated on agar. The encapsulation efficiency was 88.8 ±1.13 % and drug content 22±4% w/w. The particles had a median diameter of 2.88±0.8 µm, and appeared as collapsed spheres. Their calculated aerodynamic diameter was about 1 µm. In vitro drug release from the particles was first-order and extended beyond 10 days. Flow cytometry indicated that the particles were taken up by macrophages within 3h. Macrophages exposed to the particles or rapamycin in solution at a concentration of 100 g/ml over a 24h period maintained 79.37±0.72% and 58.33±1.39% viability respectively. Efficacy studies concluded that particles were more effective in clearing intracellular mycobacteria than rapamycin in solution. It was concluded that the preparation was suitable for formulating as a dry powder inhalation to test efficacy of inhaled, macrophage-targeted rapamycin against TB.
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| Format |
583662 bytes
application/pdf |
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| Language |
en
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| Relation |
CSIR-CDRI Communication No. 8622
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| Subject |
Autophagy
Macrophages Microspheres Inhalation Spray-Drying |
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| Title |
Inhalable Particles Containing Rapamycin for Induction of Autophagy in Macrophages Infected with Mycobacterium Tuberculosis
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| Type |
Article
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