Effect of antitubercular drugs on dipalmitoylphosphatidylcholine monolayers: implications for drug loaded surfactants.
The year long chemotherapy in pulmonary tuberculosis results in dose related side effects and may not reach atelectatic areas. On account of its spreading properties and the ability to re-expand atelectatic areas, exogenous surfactant may act as a pulmonary drug delivery agent. We investigated the interactions between antitubercular drugs and the main surfactant component, dipalmitoylphosphatidylcholine (DPPC) with the aim of developing more effective antitubercular drug loaded surfactants. The surface properties were evaluated using a Langmuir-Blodgett trough and Wilhelmy balance at 37 degrees C. Lung surfactant was modeled as DPPC monolayers. The isoniazid (INH)-DPPC combination in 1:1 ratio by weight significantly improved the adsorption of DPPC, reached a minimum surface tension of zero, formed a low compressibility film and required 32.7% area change to decrease surface tension from 30 to 10 mN/m. The triple drug (INH-rifampicin-ethambutol in 1:2:3 ratio by weight) DPPC combination when used in 1:1 or 1:2 ratios by weight also achieved surface properties superior to those of DPPC alone. A significant improvement in the adsorption was observed (surface tensions of 34.7 mN/m for 1:1 and 32.0 mN/m for 1:2 triple drug: DPPC combinations in the first second), and the films had low compressibility reaching a minimum surface tension of zero on compression. Thus, we observed statistically significant improvements in all the surface parameters and we feel encouraged to continue developing a tuberculosis therapy consisting of surfactant liposomes carrying antitubercular drugs.
Chimote
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G
School of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400 076, India.
Banerjee
R
R
D000704:Analysis of Variance; D000995:Antitubercular Agents / Q000494:pharmacology*; D004338:Drug Combinations; D004983:Ethanolamines / Q000737:chemistry / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D011663:Pulmonary Surfactants / Q000737:chemistry* / Q000378:metabolism; D013499:Surface Properties / Q000187:drug effects*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy
D000995:Antitubercular Agents; D004338:Drug Combinations; D004983:Ethanolamines; D005231:Fatty Acids, Unsaturated; D011663:Pulmonary Surfactants; C494000:dipalmitoleoylphosphatidylethanolamine