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Current HIV Research Jan 2012Here, we review the armamentarium on in vitro/ex vivo models of HIV sexual transmission and discuss how these models can be applied to study candidate microbicides. (Review)
Review
Here, we review the armamentarium on in vitro/ex vivo models of HIV sexual transmission and discuss how these models can be applied to study candidate microbicides.
Topics: Administration, Intravaginal; Administration, Rectal; Anti-Infective Agents, Local; Anti-Retroviral Agents; Cells, Cultured; Drug Design; Epithelial Cells; HIV Infections; HIV-1; Humans; Models, Biological
PubMed: 22264048
DOI: 10.2174/157016212799304661 -
Current HIV Research Jan 2012The development of pre-exposure prophylactics or microbicide products for the reduction or elimination of the sexual transmission of HIV has numerous challenges or... (Review)
Review
The development of pre-exposure prophylactics or microbicide products for the reduction or elimination of the sexual transmission of HIV has numerous challenges or barriers to success. Historically traditional dosage forms such as gels have been developed in the field but more recently controlled release dosage forms such as vaginal rings and novel dosage forms such as polymeric thin films have been studied. Studies have begun to incorporate scientific strategies into the formulation design of microbicide products in order to develop safer and more effective products. In addition advanced drug delivery strategies to overcome barriers to delivery and specific drug targeting methods are being employed. In the present review, a comprehensive discussion of formulation efforts and novel delivery strategies in the field of microbicide product development is presented.
Topics: Administration, Intravaginal; Administration, Oral; Administration, Rectal; Anti-Infective Agents, Local; Anti-Retroviral Agents; Clinical Trials as Topic; Delayed-Action Preparations; Drug Design; Drug Evaluation, Preclinical; Female; Gels; HIV Infections; Humans; Male
PubMed: 22264050
DOI: 10.2174/157016212799304599 -
Future Microbiology Jul 2011Women are now becoming pivotal in the epidemiological spread of HIV infection throughout the world, especially in developing countries, where heterosexual transmission... (Review)
Review
Women are now becoming pivotal in the epidemiological spread of HIV infection throughout the world, especially in developing countries, where heterosexual transmission accounts for more than 80% of all new HIV infections. Recently, significant but partial successes have occurred in the field of HIV prevention, including male circumcision, preventive HIV vaccines, vaginal microbicides and oral pre-exposure prophylaxis, and there is increasingly widespread access to antiretroviral treatment. However, none of the currently available tools for HIV intervention are sufficiently effective, particularly for women, and all require further development. Among all biomedical approaches, microbicides could hold the greatest hope of curtailing AIDS worldwide, especially if used by women in Africa. Research for an efficacious microbicide constitutes a priority in the global agenda to prevent HIV infection. Finally, the combination of existing partially effective strategies for HIV prevention should be promoted, scaled-up and evaluated.
Topics: Administration, Intravaginal; Anti-Infective Agents; Chemoprevention; Female; HIV Infections; Humans; Male
PubMed: 21797688
DOI: 10.2217/fmb.11.64 -
Contraception Jul 2014ACIDFORM is a candidate microbicide with spermicidal properties. A large Phase 3 trial is underway, and it is anticipated that this product will be approved for... (Review)
Review
OBJECTIVE
ACIDFORM is a candidate microbicide with spermicidal properties. A large Phase 3 trial is underway, and it is anticipated that this product will be approved for contraceptive use and marketed soon in the United States. The goal of this article is to critically review the evidence supporting the properties, safety profile and different uses of ACIDFORM gel.
STUDY DESIGN
We searched PubMed and Medline for any published literature on ACIDFORM.
RESULTS
ACIDFORM is an acidifying agent that works by lowering the vaginal pH to enhance the normal vaginal defenses. In addition to strong acid-buffering properties, ACIDFORM has high bioadhesive and viscosity-retaining properties. Several Phase 1 clinical trials have demonstrated the vaginal safety of ACIDFORM used alone or in combination with a diaphragm, although dose-dependent side effects appear to be present. Studies investigating the efficacy of ACIDFORM against sexually transmitted infections (STIs) are promising, but further trials are needed.
CONCLUSIONS
The properties of ACIDFORM offer many advantages for use, either alone or in combination with another active ingredient, such as Tenofovir. Potential applications for ACIDFORM include use as a personal lubricant, a vaginal contraceptive (alone or with a barrier method) and a microbicidal product or as a formulation vehicle for an active ingredient.
IMPLICATIONS
ACIDFORM is a candidate female-controlled vaginal preparation with microbicidal and spermicidal properties. A dual protection method could prevent unwanted pregnancies and reduce the risk of STI acquisition.
Topics: Anti-Infective Agents; Clinical Trials, Phase I as Topic; Clinical Trials, Phase III as Topic; Contraceptive Agents; Female; Humans; Male; Spermatocidal Agents; United States
PubMed: 24565736
DOI: 10.1016/j.contraception.2014.01.015 -
Sexually Transmitted Diseases Nov 2002Microbicides are being developed for woman-controlled protection against sexually transmitted diseases (STDs).
BACKGROUND
Microbicides are being developed for woman-controlled protection against sexually transmitted diseases (STDs).
GOAL
The goal of the study was to test candidate microbicides in a mouse model for preventing vaginal transmission of and for acute toxicity to columnar epithelium.
STUDY DESIGN
Progestin-sensitized CF-1 mice were treated vaginally with 50 microl of microbicide, followed either by vaginal inoculation with 10 ID(50) of serovar D or by examination of the epithelial surface for acute toxicity with a viability stain (ethidium homodimer-1).
RESULTS
Nonoxynol-9 (N9), sodium dodecyl sulfate (SDS), chlorhexidine digluconate, and BufferGel all provided significant though incomplete protection against vaginal transmission. Other candidates, all of which were effective in vitro, provided no vaginal protection: kappa-carrageenan, dextran sulfate, polystyrene sulfonate, Concanavalin A, wheat germ agglutinin, and agglutinin. The surface-active agents (N9, SDS, and chlorhexidine) caused significant acute epithelial toxicity: 3 days after chlorhexidine exposure, mice also had vaginal friability and markedly increased susceptibility to. BufferGel was the only candidate tested that was both protective and relatively nontoxic.
CONCLUSION
Microbicides can provide vaginal protection against in highly susceptible progestin-sensitized mice. Since N9 does not inactivate, it likely protects by killing target cells in the vagina. Despite the ability to both potently inactivate and kill target cells, two surface-active agents, SDS and chlorhexidine, failed to provide complete protection, a circumstance which emphasizes the importance of distributing microbicides to all susceptible surfaces.
Topics: Acrylic Resins; Administration, Intravaginal; Animals; Anti-Infective Agents, Local; Chlamydia Infections; Chlamydia trachomatis; Chlorhexidine; Disease Models, Animal; Female; Mice; Nonoxynol; Sodium Dodecyl Sulfate; Spermatocidal Agents; Treatment Outcome
PubMed: 12438901
DOI: 10.1097/00007435-200211000-00007 -
International Journal of Infectious... Oct 2011There is an urgent need to develop vaginal microbicides to empower women to better control their own sexual life and to protect themselves against HIV and other sexually... (Review)
Review
There is an urgent need to develop vaginal microbicides to empower women to better control their own sexual life and to protect themselves against HIV and other sexually transmitted infections (STIs). Prevention of STIs with its 330 million cases a year would have a great global health impact. Because of their anatomy, women are up to 8 times more susceptible than men to STIs including HIV. Women who can't negotiate condom use with their male partners have no means of protecting themselves from these infections. In the last few years, especially after the recent failures of several microbicides in Phase III trials, there was increasing pressure from those favoring the use of a more targeted approach to introduce marketed antiretroviral drugs (ARVs) into microbicides. This Pre-Exposure Prophylaxis (PrEP) concept which targets only HIV using specific ARVs contrasts with the primary approach of broad spectrum microbicides which aimed at offering universal protection against several sexually transmitted pathogens. However, before using ARVs as PrEP for HIV prevention, there are still many important issues to consider. In this article, we compare both strategies, while reviewing the last 15 years of microbicide research and its future.
Topics: Anti-Infective Agents; Anti-Retroviral Agents; Antibiotic Prophylaxis; Female; HIV Infections; Humans; Male; Sexually Transmitted Diseases; Treatment Failure
PubMed: 21705253
DOI: 10.1016/j.ijid.2011.05.001 -
Nanotechnology Feb 2017The vaginal route is increasingly being considered for both local and systemic delivery of drugs, especially those unsuitable for oral administration. One of the... (Review)
Review
The vaginal route is increasingly being considered for both local and systemic delivery of drugs, especially those unsuitable for oral administration. One of the opportunities offered by this route but yet to be fully utilised is the administration of microbicides. Microbicides have an unprecedented potential for mitigating the global burden from HIV infection as heterosexual contact accounts for most of the new infections occurring in sub-Saharan Africa, the region with the highest prevalent rates. Decades of efforts and massive investment of resources into developing an ideal microbicide have resulted in disappointing outcomes, as attested by several clinical trials assessing the suitability of those formulated so far. The highly complex and multi-level biochemical interactions that must occur among the virus, host cells and the drug for transmission to be halted means that a less sophisticated approach to formulating a microbicide e.g. conventional gels, etc may have to give way for a different formulation approach. Nanotechnology has been identified to offer prospects for fabricating structures with high capability of disrupting HIV transmission. In this review, predominant challenges seen in microbicide development have been highlighted and possible ways of surmounting them suggested. Furthermore, formulations utilising some of these highly promising nanostructures such as liposomes, nanofibres and nanoparticles have been discussed. A perspective on how a tripartite collaboration among governments and their agencies, the pharmaceutical industry and academic scientists to facilitate the development of an ideal microbicide in a timely manner has also been briefly deliberated.
Topics: Administration, Intravaginal; Anti-Infective Agents; Contraceptive Devices, Female; Drug Industry; Female; Government Agencies; HIV Infections; Humans; Liposomes; Nanofibers; Nanoparticles; Nanotechnology; Public-Private Sector Partnerships; Vagina
PubMed: 28032619
DOI: 10.1088/1361-6528/28/5/052001 -
Social Science & Medicine (1982) Aug 2006Qualitative research was conducted in South Africa to determine perceptions about intra-vaginal microbicides in order to better understand the socioeconomic, cultural...
Qualitative research was conducted in South Africa to determine perceptions about intra-vaginal microbicides in order to better understand the socioeconomic, cultural and structural contexts for the support of future introduction of this new HIV prevention method. Focus group discussions and in-depth interviews were conducted at community, health service, and policy levels of inquiry. The main study site was a black working class urban area close to Cape Town. "Desperation" in response to the HIV/AIDS epidemic, rape, sexual coercion and unplanned consensual sex emerged as major reasons to support microbicides, while concerns about the partial effectiveness of microbicide protection and its hypothetical nature elicited a more cautious approach. Other key findings included the likelihood that microbicides would be "mainstream", the possible impact on sexual practices and gender norms, issues of condom substitution/migration and potential avenues for education and distribution. We found that microbicides have the potential to meet diverse needs beyond that suggested by prior research. This included a desire for products that could protect against HIV infection following rape, sexual coercion and unplanned sex, and the finding that a wider range of people than previously suggested would potentially use microbicides. The challenge for microbicide introduction will be to develop products that can meet diverse needs not only in South Africa, but also in the broader global context.
Topics: Adolescent; Adult; Anti-Infective Agents, Local; Attitude to Health; Female; Focus Groups; HIV Infections; Humans; Interviews as Topic; Male; Middle Aged; Sexually Transmitted Diseases, Viral; South Africa; Urban Health; Vaginal Creams, Foams, and Jellies
PubMed: 16600447
DOI: 10.1016/j.socscimed.2006.02.019 -
BioMed Research International 2015Bioactive peptides are part of an innate response elicited by most living forms. In plants, they are produced ubiquitously in roots, seeds, flowers, stems, and leaves,... (Review)
Review
Bioactive peptides are part of an innate response elicited by most living forms. In plants, they are produced ubiquitously in roots, seeds, flowers, stems, and leaves, highlighting their physiological importance. While most of the bioactive peptides produced in plants possess microbicide properties, there is evidence that they are also involved in cellular signaling. Structurally, there is an overall similarity when comparing them with those derived from animal or insect sources. The biological action of bioactive peptides initiates with the binding to the target membrane followed in most cases by membrane permeabilization and rupture. Here we present an overview of what is currently known about bioactive peptides from plants, focusing on their antimicrobial activity and their role in the plant signaling network and offering perspectives on their potential application.
Topics: Anti-Infective Agents; Hydrolysis; Peptides; Plants; Signal Transduction
PubMed: 25815307
DOI: 10.1155/2015/102129 -
Therapeutic Delivery Dec 2011The HIV/AIDS pandemic continues to be a global health priority, with high rates of new HIV-I infections persisting in young women. One HIV prevention strategy is topical... (Review)
Review
The HIV/AIDS pandemic continues to be a global health priority, with high rates of new HIV-I infections persisting in young women. One HIV prevention strategy is topical pre-exposure prophylactics or microbicides, which are applied vaginally or rectally to protect the user from HIV and possibly other sexually transmitted infections. Vaginal microbicide delivery will be the focus of this review. Multiple nonspecific and specific antiretroviral microbicide products have been clinically evaluated, and many are in preclinical development, The events of HIV mucosal transmission and dynamics of the cervicovaginal environment should be considered for successful vaginal microbicide delivery. Beyond conventional vaginal formulations, intravaginal rings, tablets and films are employed as platforms in the hope to increase the likelihood of microbicide use. Furthermore, combining multiple antiretrovirals within a given formulation, combining a microbicide product with a vaginal device and integrating novel drug-delivery strategies within a microbicide product are approaches to successful vaginal-microbicide delivery.
Topics: Administration, Intravaginal; Anti-Infective Agents, Local; Anti-Retroviral Agents; Clinical Trials as Topic; Female; HIV Infections; Humans; Vagina
PubMed: 22468220
DOI: 10.4155/tde.11.126