Permeability of tritiated water through human cervical and vaginal tissue

Sassi, Alexandra B.; McCullough, Kristy D.; Cost, Marilyn; Hillier, Sharon L.; Rohan, Lisa C.

doi:10.1002/jps.20107

Cited by 39 publications

(34 citation statements)

References 25 publications

(51 reference statements)

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“…Assuming that ARV-based microbicides will be low-risk is reasonable because systemic absorption has not been found in phase I trials of intravaginal application of ARV-based microbicides (e.g., tenofovir, UC-781, and TMC-120) (3,11,12). However, assuming that they will be high-risk is also reasonable because the vagina is highly permeable (13)(14)(15)(16) and is often an ideal route for drug administration (17)(18)(19)(20)(21). Hence, in all of our analyses, we investigate the potential impact of both types of microbicides.…”

Section: The Paradoxical Effects Of Using Antiretroviral-based Microbmentioning

confidence: 99%

The paradoxical effects of using antiretroviral-based microbicides to control HIV epidemics

Wilson

Coplan

Wainberg

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Vaginal microbicides, designed to prevent HIV infection in women, are one of the most promising biomedical interventions. Clinical trials of second-generation microbicides have begun; if shown to be effective, they could be licensed within 5–10 years. Because these microbicides contain antiretrovirals (ARVs), they could be highly effective. However, there is concern that, if used by HIV-positive women, ARV resistance may evolve. By analyzing a mathematical model, we find that adherence could have both beneficial and detrimental effects on trial outcomes. Most importantly, we show that planned trial designs could mask resistance risks and therefore enable high-risk microbicides to pass clinical testing. We then parameterize a transmission model using epidemiological, clinical, and behavioral data to predict the consequences of wide-scale usage of high-risk microbicides in a heterosexual population. Surprisingly, we show that reducing a participant's risk of resistance during a trial could lead to unexpectedly high rates of resistance afterward when microbicides are used in public health interventions. We also find that, paradoxically, although microbicides will be used by women to protect themselves against infection, they could provide greater benefit to men. More infections in men than in women will be prevented if there is a high probability that ARVs are systemically absorbed, microbicides are less than ∼50% effective, and/or adherence is less than ∼60%. Men will always benefit more than women in terms of infections prevented per resistant case; but this advantage decreases as the relative fitness of drug-resistant strains increases. Interventions that use ARV-based microbicides could have surprising consequences.

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Section: The Paradoxical Effects Of Using Antiretroviral-based Microbmentioning

confidence: 99%

The paradoxical effects of using antiretroviral-based microbicides to control HIV epidemics

Wilson

Coplan

Wainberg

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…The thickness of the tissue was determined to be ranging from 900 to 1140 189 microns. It was earlier confirmed that no significant differences were observed in using 190 fresh or snap-frozen tissue samples (Sassi et al, 2004 …”

Section: Preparation Of Vaginal Tissue 183mentioning

confidence: 78%

Chitosan-coated liposomes for topical vaginal therapy: Assuring localized drug effect

Jøraholmen

Vanić

Tho

et al. 2014

International Journal of Pharmaceutics

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16The choice of drug therapy in pregnant patients suffering from vaginal infections is limited 17 by the safety profile of the drug. Assuring the efficient topical therapy to avoid systemic 18 absorption is considered the best therapy option. Chitosan-coated liposomes have been 19 developed and optimized to assure localized therapy of clotrimazole. Chitosan was selected 20 as mucoadhesive polymer both to prolong system's retention at the vaginal site and act on 21 biofilms responsible for high recurrence of infections. Sonicated liposomes were coated 22 with chitosan in three different concentrations, namely 0.1, 0.3 and 0.6 % (w/v).

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“…In this study, an in vitro three-dimensional OMM was used for quantitative analysis of the BS of the Ti -OME interface. Permeability tests have been used in studies such as the investigation of the barrier properties of different tissues for drug delivery routes [21,22]. To our knowledge, this is the first time a permeability test has been used to evaluate the BS of different Ti surface topographies using a three-dimensional OMM.…”

Section: Discussionmentioning

confidence: 99%

“…In order to achieve a peripheral seal, all the samples were clamped between the two compartments of an insert, a method used in other studies [21][22][23]. The use of adhesive to form the peripheral seal has been reported in another study on biopsied tissues [23].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The biological seal of the implant–soft tissue interface evaluated in a tissue-engineered oral mucosal model

Chai

Brook

Palmquist

et al. 2012

J. R. Soc. Interface.

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For dental implants, it is vital that an initial soft tissue seal is achieved as this helps to stabilize and preserve the peri-implant tissues during the restorative stages following placement. The study of the implant -soft tissue interface is usually undertaken in animal models. We have developed an in vitro three-dimensional tissue-engineered oral mucosal model (3D OMM), which lends itself to the study of the implant -soft tissue interface as it has been shown that cells from the three-dimensional OMM attach onto titanium (Ti) surfaces forming a biological seal (BS). This study compares the quality of the BS achieved using the threedimensional OMM for four types of Ti surfaces: polished, machined, sandblasted and anodized (TiUnite). The BS was evaluated quantitatively by permeability and cell attachment tests. Tritiated water (HTO) was used as the tracing agent for the permeability test. At the end of the permeability test, the Ti discs were removed from the three-dimensional OMM and an Alamar Blue assay was used for the measurement of residual cells attached to the Ti discs. The penetration of the HTO through the BS for the four types of Ti surfaces was not significantly different, and there was no significant difference in the viability of residual cells that attached to the Ti surfaces. The BS of the tissue-engineered oral mucosa around the four types of Ti surface topographies was not significantly different.

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Permeability of tritiated water through human cervical and vaginal tissue

Cited by 39 publications

References 25 publications

The paradoxical effects of using antiretroviral-based microbicides to control HIV epidemics

The paradoxical effects of using antiretroviral-based microbicides to control HIV epidemics

Chitosan-coated liposomes for topical vaginal therapy: Assuring localized drug effect

The biological seal of the implant–soft tissue interface evaluated in a tissue-engineered oral mucosal model

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