Evaluation of dodecylmaltoside as a permeability enhancer for insulin using human carcinoma cells.
Dodecylmaltoside (DDM), an alkylglycoside showing tissue-permeability-enhancing properties, has been successful in improving nasal and ocular transport of poorly absorbed drugs. It was hypothesized that optimization of DDM concentration would improve the transport of insulin across epithelial monolayers without causing cell damage. Samples of markers and insulin were collected over a 6-h period and transepithelial electrical resistance was measured at concurrent time points to ascertain the effect of DDM on tight junctions. Samples were analyzed for lucifer yellow and insulin using reversed-phase high-performance liquid chromatography and for (3)[H]-mannitol by scintillation counting. A significant increase in the transport of markers and insulin was recorded in DDM-treated cells compared with controls. DDM enhanced the transport of markers and insulin in a concentration-dependent manner. Decreased transepithelial electrical resistance values confirmed that enhanced transport is caused by loosening of tight junctions. Cell recovery was >95% in 8 h indicating the potential of DDM as a penetration enhancer for clinical administration of insulin and other poorly absorbed drugs without causing cell damage.
Tirumalasetty
Phani Prasanth
PP
Harrison School of Pharmacy, Auburn University, Auburn, Alabama 36849, USA.
Eley
John G
JG
D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D017097:Electric Impedance; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005456:Fluorescent Dyes; D006027:Glycosides / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D007328:Insulin / Q000493:pharmacokinetics* / Q000494:pharmacology; D007546:Isoquinolines; D013997:Time Factors
D005456:Fluorescent Dyes; D006027:Glycosides; D007004:Hypoglycemic Agents; D007328:Insulin; D007546:Isoquinolines; C017475:lucifer yellow