Document Detail


The safety of ethambutol dihydrochloride dry powder formulations containing chitosan for the possibility of treating lung tuberculosis.
MedLine Citation:
PMID:  25472479     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
MATERIALS AND METHODS: Nanosized drug particles were prepared by optimizing the spray drying conditions. The cell toxicities were determined by interacting the formulations with respiratory cell lines (A549, calu-3 and NR8383 cell lines), and phagocytosis of the formulations was tested on a macrophage cell line. Permeations of the EDH formulations across a lipid bilayer were studied using the Ussing chamber and HPLC. Bioactivity tests of the formulations were carried out by using the resazurin method on M. bovis cells.
RESULT AND DISCUSSION: Spray rate and inlet temperature were the two most important factors that affected the size and % yield of the product. The % cell viability of A549 cells with all EDH formulations, pure EDH and chitosan carrier was higher than 80%, the calu-3 cell line had % viabilities of between 85 and 99%, and the % viability of NR8383 cells was between 81 and 100%. The pure EDH had a minimum inhibitory concentration (MIC) of 2 µg/mL while the EDH formulations had MIC values of less than 1 µg/mL when tested against M. bovis. The formulation was completely phagocytized by the macrophage cells after 30 min. The permeability of pure EDH across lipid bilayer was 48.7% after 2 h while in the EDH formulations it was enhanced to 71%.
CONCLUSION: The EDH formulations showed a lower toxicity, higher potency and better permeation than the pure EDH. Thus, EDH DPI formulations could help to minimize the duration of treatment and the risk of developing multidrug resistance tuberculosis compared to the non-formulated EDH.
Authors:
Md Iftekhar Ahmad; Titpawan Nakpheng; Teerapol Srichana
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Inhalation toxicology     Volume:  26     ISSN:  1091-7691     ISO Abbreviation:  Inhal Toxicol     Publication Date:  2014 Dec 
Date Detail:
Created Date:  2014-12-04     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8910739     Medline TA:  Inhal Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  908-17     Citation Subset:  IM    
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