Vaginal epithelium permeability

Vaginal Rings. Vaginal epithelium is readily permeable to contraceptive steroids. Since the vascular drainage of the vagina bypasses the Hver, this route of adrninistration potentially permits utilisation of dmgs that have low oral activity. 

A more permeable epithelium obviously facilitates greater absorption. Some epithelia are relatively more permeable than others. For example, the skin is an extremely impermeable barrier, whereas the permeability of the lung membranes towards many compounds is much higher than the skin and is also higher than that of the small intestine and other mucosal routes. The vaginal epithelium is relatively permeable, particularly at certain stages of the menstrual cycle. 

In postmenopausal women, the incidence of mitosis in the basal and parabasal layers and the number of small blood vessels decreases. The vaginal epithelium becomes extremely thin, cell boundaries in the surface are less distinct, the micro-ridges of the cells are dramatically reduced, and the vagina is often invaded with leukocytes. Naturally, this thinning of the epithelium leads to a substantial increase in the permeability of this tissue. 

However, these general observations do not take into account the cyclical changes in the vaginal epithelium, which exert profound effects on vaginal absorption, especially for hydrophilic compounds. The permeability coefficient for the vaginal membrane (Pm) is equal to the sum of the permeability coefficient through the lipid pathway (P ) and the pore pathway (Pp) ... 

Although, as described above, the vagina is permeable to many peptides and proteins, in most cases the bioavailability is insufficient for systemic therapy and is also highly variable. Penetration enhancers may be used to promote peptide absorption across the vaginal epithelium. However, less extensive investigations on the use of penetration enhancers for the vaginal route have been carried out in comparison to other routes, such as intranasal and transdermal (see Sections 9.7.1 and 8.6.1). 

Unlike other tissues, the vagina is greatly affected by steroid replacement therapy. Estrogen replacement therapy is often used to treat menopausal symptoms. The postmenopausal state of the vaginal epithelium, with its thinner epithelium and increased permeability, is an important consideration in drug delivery. The minimization of epithelial fluctuation will result in less fluctuation in absorption, affecting both systemic and local drug deliveries. 

FIGURE 22.6 Permeability and permselectivity of vaginal and buccal epithelia in the rabbit, (a) Flux of 6-carboxyfluoroscein, a hydrophilic molecule, by in vitro perfusion studies steady-state flux ( xg/cm2/h x 106), (b) resistance (fl cm2 x 10 2), (c) thickness (p,m x 10-2), and (d) ratio of potassium transport number to chloride transport number, which is calculated from electrical measurements, used as indicative of the epithelium selectivity for positively charged molecules. (Modified from Sayani, A.P. and Chien, Y.W., Crit. Rev. Ther. Drug Carrier Syst. 13, 85, 1996.)... 

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