The role of surfactant in, and a comparison of, the permeability of porcine and human epithelia to various chemical compounds

[摘要] In this thesis, research results are reported on the role of natural and syntheticsurfactants on the in vitro permeability characteristics of various chemicalcompounds across porcine (buccal, bronchial, arterial, venous and rectal) andhuman (vaginal) tissues. The permeability flux values of the differentcompounds (arecoline, 17β-estradiol, hydrocortisone, dexamethasone,vasopressin, oxytocin, zidovudine and isoniazid) were determined using acontinuous flow-through diffusion system. Mean steady state flux values werecompared statistically by means of a t-test at a significance level of 5% as wellas an F-test using whole curve comparisons. The results indicated that thesynthetic pulmonary surfactant Biopolsurf is an effective enhancer for thepermeation of chemical compounds through most of the tissues tested andthat molecular weight, electrostatic charge, partitioning of the molecules insurfactant and surfactant concentration play an important role in transmembrane diffusion.In addition the epithelial permeability of the different types of tissues forvarious chemical compounds (arecoline, 17β-estradiol, hydrocortisone,dexamethasone, vasopressin and oxytocin) across the above tissues werecompared. The results obtained showed that the permeability flux values ofthe compounds across porcine bronchial and human vaginal tissues wereconsistently similar and that porcine buccal tissue had the lowest permeabilityof all tissues tested. This was in agreement with previous in vitro studies. Itwas concluded that a wide variation in the permeability characteristics ofdifferent epithelia exists and that the pulmonary epithelium, due to its highpermeability, is probably the most effective epithelium for drug deliverypurposes, especially for drugs that undergo extensive gastrointestinal orhepatic first-pass metabolism.

[发布机构] Stellenbosch University