Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
602310 | Colloids and Surfaces B: Biointerfaces | 2008 | 7 Pages |
Abstract
Insertion profiles of antitubercular drugs isoniazid (INH), rifampicin (RFM) and ethambutol (ETH) into dipalmitoylphosphatidylcholine (DPPC) membrane models were evaluated by Langmuir monolayer technique. Maximum drug insertion into DPPC monolayer was observed with rifampicin with a surface pressure increase (ÎÏmax) in the range of 21-33Â mN/m depending upon rifampicin concentration. Isoniazid had minimal insertion resulting in a lower ÎÏmax of about 2-3Â mN/m, suggestive of minimal interactions between INH and DPPC. Ethambutol surface pressure increment on insertion resulted in an intermediate rise in the ÎÏmax (6-10Â mN/m). Antitubercular drug combination in the ratio of 2Â mM:0.7Â mM:4.5Â mM for INH:RFM:ETH, attained ÎÏmax between 25 and 33Â mN/m. Insertion profiles similar to rifampicin were exhibited by the antitubercular drug mixture suggestive of predominant rifampicin insertion into the DPPC monolayer. The extent of drug insertion into the DPPC monolayer is suggestive of the drug penetration potential into biological membranes in vivo. Higher RFM ÎÏmax is suggestive of excellent cell membrane penetration, which explains broad reach of the drug to all the organs including the cerebrospinal fluid while lower ÎÏmax of INH suggests poor membrane penetration restricting the entry of the drug in different biological membranes. DPPC membrane destabilization was observed at higher antitubercular drug concentrations indicated by the negative slopes of the surface pressure-time curves. This may correlate with the dose related toxic effects observed in tuberculosis affected patients. Drug insertion studies offer a potential tool in understanding the pharmacotoxicological behavior of the various pharmacological agents.
Related Topics
Physical Sciences and Engineering
Chemical Engineering
Colloid and Surface Chemistry
Authors
G. Chimote, R. Banerjee,