Intravaginal Gels as Drug Delivery Systems

Justin-Temu, M; Damian, F.; Kinget, Renaat; Mooter, Guy Van den

doi:10.1089/jwh.2004.13.834

Cited by 52 publications

(35 citation statements)

References 50 publications

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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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“…In addition, systemic medications can lead to significant adverse side effects when high drug concentrations in the circulation are required to elicit a therapeutic response in the CV tract (5). To reduce side effects and achieve localized therapy, recent efforts have increasingly emphasized topical drug delivery methods, such as creams, hydrogels, and inserted devices, to deliver therapeutics to the apical side of the cervix epithelium (6)(7)(8)(9)(10)(11). Apical drug delivery may also be extended to protection against sexual transmission of infections, because neutralizing antibodies and microbicides must act at mucosal surfaces to block the entry of pathogens (12)(13)(14)(15).…”

mentioning

confidence: 99%

Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus

Lai¹,

O’Hanlon

Harrold

et al. 2007

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

897

1,012

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Nanoparticles larger than the reported mesh-pore size range (10 -200 nm) in mucus have been thought to be much too large to undergo rapid diffusional transport through mucus barriers. However, large nanoparticles are preferred for higher drug encapsulation efficiency and the ability to provide sustained delivery of a wider array of drugs. We used high-speed multiple-particle tracking to quantify transport rates of individual polymeric particles of various sizes and surface chemistries in samples of fresh human cervicovaginal mucus. Both the mucin concentration and viscoelastic properties of these cervicovaginal samples are similar to those in many other human mucus secretions. Unexpectedly, we found that large nanoparticles, 500 and 200 nm in diameter, if coated with polyethylene glycol, diffused through mucus with an effective diffusion coefficient (D eff) only 4-and 6-fold lower than that for the same particles in water (at time scale ‫؍‬ 1 s). In contrast, for smaller but otherwise identical 100-nm coated particles, D eff was 200-fold lower in mucus than in water. For uncoated particles 100 -500 nm in diameter, D eff was 2,400-to 40,000-fold lower in mucus than in water. Much larger fractions of the 100-nm particles were immobilized or otherwise hindered by mucus than the large 200-to 500-nm particles. Thus, in contrast to the prevailing belief, these results demonstrate that large nanoparticles, if properly coated, can rapidly penetrate physiological human mucus, and they offer the prospect that large nanoparticles can be used for mucosal drug delivery. drug delivery ͉ mucosal tissues ͉ particle tracking ͉ PEG

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“…Pharmaceutical gel preparations such as hydrogels, organogels, and emulgels have been extensively used to deliver both hydrophilic and lipophilic drugs for dermatological and transdermal use. Gels are crosslinked assembly containing both solid and liquid components within its configuration, which were considered as gelling agents and called gelators [2]. When the gelators are dispersed in appropriate solvent, they were associated together forming network of three-dimensional structure, which immobilize the surrounding aqueous media [2].…”

Section: Introductionmentioning

confidence: 99%

“…Gels are crosslinked assembly containing both solid and liquid components within its configuration, which were considered as gelling agents and called gelators [2]. When the gelators are dispersed in appropriate solvent, they were associated together forming network of three-dimensional structure, which immobilize the surrounding aqueous media [2]. These results are followed by a series of the interactions to form the polymeric cross-linked network structures, which retained certain amount of the water [3].…”

Section: Introductionmentioning

confidence: 99%

Hydrogels and Their Combination with Liposomes, Niosomes, or Transfersomes for Dermal and Transdermal Drug Delivery

Ibrahim¹,

Nair²,

Al‐Dhubiab³

et al. 2017

Liposomes

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Polymeric networks that retain and absorb substantial amount of water or biological fluids and resemble as a biological tissue are defined as hydrogels. On the other hand, liposomes, transfersomes and niosomes are lipid carriers, which represent one of the major research and development focus areas of the pharmaceutical industry. They have great potential as lipid vehicles that are able to enhance permeation of drugs across the intact skin and can act as local depot for the drug to sustain and control its delivery. Lipid carrier and hydrogel combinations offer transdermal drug delivery of great potential to enhance systemic effects of both hydrophilic and lipophilic drugs. Also, lipid carriers can target drugs to skin appendages and improve transdermal delivery. Lipid carrier proform systems in the form of gelly liquid crystals can also be used transdermally for better drug absorption enhancement. This review highlights the potential of hydrogels and emulgels with or without lipid nanocarriers for dermal and transdermal application.

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Intravaginal Gels as Drug Delivery Systems

Cited by 52 publications

References 50 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

Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus

Hydrogels and Their Combination with Liposomes, Niosomes, or Transfersomes for Dermal and Transdermal Drug Delivery

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