Permeation of 17β-estradiol through human vaginal and buccal mucosa

Bijl, Pieter van der; Eyk, A D van; Thompson, I O

doi:10.1016/s1079-2104(98)90063-4

Cited by 43 publications

(29 citation statements)

References 14 publications

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“…Although this route offers a gender-specific treatment of systemic or local, female-related conditions (2,3), the merits of vaginal administration such as the avoidance of hurdles associated with per-oral or parenteral application (i.e., drug hepatotoxicity, first-pass drug metabolism, drug plasma concentrations fluctuations, side effects, inconvenience, irritation of gastrointestinal mucosa; 2) enable prolonged dosing with lower daily doses of drugs applied in controlled-release delivery systems (1). Achieving comparable pharmacodynamic effects by vaginal route as by per-oral drug delivery provides indirect proof of effective drug absorption through vaginal mucosa owing to its high absorptive surface area, rich blood supply, significantly diminished expression of phase I and II metabolizing enzymes and transporters, and sufficient permeability to drugs (4)(5)(6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Development and Evaluation of an In Vitro Vaginal Model for Assessment of Drug’s Biopharmaceutical Properties: Curcumin

et al. 2012

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Abstract. Vaginal administration is a promising alternative to the per-oral route in achieving systemic or local therapeutic effects, when intestinal drug absorption is hindered by problematic biopharmaceutical drug properties. The aim of this study was to establish an in vitro vaginal model and use it to characterize biopharmaceutical properties of liposomally associated curcumin destined for vaginal delivery. The in vitro permeability, metabolism, and tissue retention of high/low permeable compounds were assessed on cow vaginal mucosa and compared to the permeabilities determined through Caco-2 cells and rat jejunum in vitro. The results showed that the intestinal mucosa was superior to the vaginal one in categorizing drugs based on their permeabilities in high/low permeable classes. Passive diffusion was found to be the main mechanism of drug penetration through vaginal mucosa and it was not affected by transporterenzyme alliance, as their expression/activity was significantly reduced compared to the intestinal tract. Curcumin permeability from the solution form was the lowest of all tested substances due to its significant tissue retention and curcumin-mucus interactions. The permeability of liposomally associated curcumin was even lower but the binding of liposomally associated curcumin to the vaginal tissue was significantly higher. The permeability and tissue retention of liposomal curcumin were vesicle size dependent. Vaginal application of liposomally associated curcumin provides relatively high levels of curcumin in vaginal tissue, with limited systemic absorption.

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Section: Introductionmentioning

confidence: 99%

Development and Evaluation of an In Vitro Vaginal Model for Assessment of Drug’s Biopharmaceutical Properties: Curcumin

et al. 2012

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“…All the specimens were placed in a transport fluid, prepared as previously described and transferred to our laboratory within I h (17). Excess connective and adipose tissue were carefully removed from all specimens, and hereafter these were snap-frozen in liquid nitrogen and stored at -85°C.…”

Section: Human Vaginal Mucosamentioning

confidence: 99%

Physicochemical Characteristics of Molecules and Their Diffusion across Human Vaginal Mucosa

2008

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The diffusion rate of permeant molecules through mucosal tissue depends on the physicochemical characteristics of the molecules themselves as well as the properties of the tissue. In this study the diffusion kinetics of various molecules was examined through intact as well as de-epithelialised human vaginal mucosa. The molecules studied included tritium-labelled water, 17β-estradiol, reduced-arecoline, vasopressin, oxytocin, bradykinin, tacrolimus, cyclosporin A, dihydro-alprenolol, cimetidine and benzylpenicillin. Freshly harvested human vaginal tissue was frozen in liquid nitrogen and stored at −85°C. A flow-through diffusion apparatus was used for the in vitro permeability studies (24 h, 20°C, 1.5 ml/h). The mean estimated – or mean steady-state flux values for all the molecules studied across intact human vaginal mucosa, were generally found to be lower than those of the corresponding de-epithelialised tissue. Using an F-test and comparing whole curves, statistically significant differences in the diffusion rates of tacrolimus, reduced-arecoline, vasopressin, bradykinin, benzylpenicillin, water and cimetidine were found when comparing intact and de-epithelialised vaginal mucosa. Generally, smaller permeant molecules diffused at a higher rate than larger molecules. The epithelial layer retarded the diffusion rate of molecules carrying charges at physiological pH. Damage to the epithelial layer did not necessarily increase the diffusion rate of all molecules tested and small lipophilic molecules did not necessarily diffuse at higher rates than hydrophilic molecules.

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“…The frozen samples were thawed in PBS (phosphate-buffered saline) for at least 10 min. Fresh and thawed tissue disks were mounted in flow-through diffusion cells (exposed areas 0.039 B 0.001 SD cm 2 ) as previously described [13,14], and permeation studies were performed on 7 tissue replicates for each patient. Prior to commencement of the experiment, tissue disks were equilibrated for 10 min with PBS (pH 7.9) at 20°C in both the donor and receiver compartments of the diffusion cells.…”

Section: Permeability Experimentsmentioning

confidence: 99%

“…The objective of this study was to determine the barrier properties to water of fresh and frozen human skin treated with two different barrier creams containing a waterrepellant and a water-attracting base, using a continuous flow-through diffusion apparatus for small tissue samples, previously employed for determining the permeability of mucosae and synthetic membranes to a variety of compounds [13][14].…”

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confidence: 99%

Diffusion of Water across Human Skin in the Presence of Two Barrier Creams

Bijl

Eyk²,

Cilliers³

et al. 2000

Skin Pharmacol Physiol

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The in vitro permeability of tritiated water through fresh and frozen human skin was evaluated in the presence and absence of two different barrier creams. Treated (10 min) and untreated fresh and frozen human skin disks (4 mm in diameter) were mounted in flow cells of a continuous flow-through diffusion apparatus. Buffer/tritiated water was collected from the acceptor chambers at 2-hour intervals for a total of 20 h and counted in a liquid scintillation counter. The results indicated that both barrier creams lowered the average flux rates of tritiated water through fresh and frozen skin, but no significant differences could be detected between the two preparations. However, different results may be obtained when compounds with molecular weights much higher than water are used.

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Permeation of 17β-estradiol through human vaginal and buccal mucosa

Cited by 43 publications

References 14 publications

Development and Evaluation of an In Vitro Vaginal Model for Assessment of Drug’s Biopharmaceutical Properties: Curcumin

Development and Evaluation of an In Vitro Vaginal Model for Assessment of Drug’s Biopharmaceutical Properties: Curcumin

Physicochemical Characteristics of Molecules and Their Diffusion across Human Vaginal Mucosa

Diffusion of Water across Human Skin in the Presence of Two Barrier Creams

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