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Marine Drugs 2011Bacterial biofilms are surface-attached communities of microorganisms that are protected by an extracellular matrix of biomolecules. In the biofilm state, bacteria are... (Review)
Review
Bacterial biofilms are surface-attached communities of microorganisms that are protected by an extracellular matrix of biomolecules. In the biofilm state, bacteria are significantly more resistant to external assault, including attack by antibiotics. In their native environment, bacterial biofilms underpin costly biofouling that wreaks havoc on shipping, utilities, and offshore industry. Within a host environment, they are insensitive to antiseptics and basic host immune responses. It is estimated that up to 80% of all microbial infections are biofilm-based. Biofilm infections of indwelling medical devices are of particular concern, since once the device is colonized, infection is almost impossible to eliminate. Given the prominence of biofilms in infectious diseases, there is a notable effort towards developing small, synthetically available molecules that will modulate bacterial biofilm development and maintenance. Here, we highlight the development of small molecules that inhibit and/or disperse bacterial biofilms specifically through non-microbicidal mechanisms. Importantly, we discuss several sets of compounds derived from marine sponges that we are developing in our labs to address the persistent biofilm problem. We will discuss: discovery/synthesis of natural products and their analogues-including our marine sponge-derived compounds and initial adjuvant activity and toxicological screening of our novel anti-biofilm compounds.
Topics: Animals; Anti-Infective Agents; Biofilms; Biofouling; Porifera
PubMed: 22073007
DOI: 10.3390/md9102010 -
BMC Public Health Dec 2023Rectal microbicides (RM) are biomedical HIV prevention products that aim to prevent or reduce the transmission of HIV and other sexually transmitted infections (STIs).... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Rectal microbicides (RM) are biomedical HIV prevention products that aim to prevent or reduce the transmission of HIV and other sexually transmitted infections (STIs). RM modalities may be beneficial for populations who have complex lifestyles, difficulties adhering to pre-exposure prophylaxis (PrEP) regimens, and/or have limited access to care. MTN-035 (DESIRE; Developing and Evaluating Short-Acting Innovations for Rectal Use), a randomized crossover trial, aimed to evaluate the safety and acceptability of, and adherence to, three placebo RM modalities (douche, insert, and suppository) prior to receptive anal intercourse.
METHODS
We conducted latent trajectory analysis to identify clusters of individuals who shared similar trajectories in acceptability and adherence for each product (douche, insert, and suppository) over time. We analyzed weekly short messaging service (SMS) use reports for each modality as reported by enrolled sexual and gender minority (SGM) participants.
RESULTS
Two trajectories for each product were identified: a "protocol compliant" trajectory (i.e., at least one product use occasion per week) and "high use" trajectory (i.e., more than three product use occasions per week). Participants with high use were more likely to lack access to PrEP and have higher intentions to utilize RM modalities compared to those who were protocol compliant.
CONCLUSIONS
This study highlighted high adherence to RM modalities among SGM. As research into viable HIV prevention modalities continues to evolve, tailored intervention strategies are needed to support the uptake of and adherence to alternative prevention modalities that are behaviorally congruent with targeted users.
TRIAL REGISTRATION
NCT03671239 (14/09/2018).
Topics: Humans; Male; HIV Infections; Cross-Over Studies; Sexual Behavior; Sexual and Gender Minorities; Anti-Infective Agents; Homosexuality, Male; Pre-Exposure Prophylaxis; Anti-HIV Agents
PubMed: 38066471
DOI: 10.1186/s12889-023-17368-y -
Trends in Microbiology Aug 2012The development of efficient microbicides, the topically applied compounds that protect uninfected individuals from acquiring HIV-1, is a promising strategy to contain... (Review)
Review
The development of efficient microbicides, the topically applied compounds that protect uninfected individuals from acquiring HIV-1, is a promising strategy to contain HIV-1 epidemics. Such microbicides should of course possess anti-HIV-1 activity, but they should also act against other genital pathogens, which facilitate HIV-1 transmission. The new trend in microbicide strategy is to use drugs currently used in HIV-1 therapy. The success of this strategy is mixed so far and is impaired by our limited knowledge of the basic mechanisms of HIV-1 transmission as well as by the inadequacy of the systems in which microbicides are tested in preclinical studies.
Topics: Administration, Topical; Anti-Infective Agents; Drug Discovery; HIV Infections; HIV-1; Humans
PubMed: 22705107
DOI: 10.1016/j.tim.2012.05.005 -
Human Reproduction (Oxford, England) Oct 2022Is 17BIPHE2, an engineered cathelicidin antimicrobial peptide with low susceptibility to proteases, a better spermicide in cervicovaginal fluid (CVF) than its parental...
STUDY QUESTION
Is 17BIPHE2, an engineered cathelicidin antimicrobial peptide with low susceptibility to proteases, a better spermicide in cervicovaginal fluid (CVF) than its parental peptides, LL-37 and GF-17?
SUMMARY ANSWER
At the same mass concentration, 17BIPHE2 exhibited the highest spermicidal activity on human sperm resuspended in CVF-containing medium.
WHAT IS KNOWN ALREADY
LL-37 and its truncated peptide GF-17 exert both spermicidal and microbicidal activities, although they are prone to proteolytic degradation in body fluids.
STUDY DESIGN, SIZE, DURATION
Spermicidal activities of 17BIPHE2 were evaluated in vitro in mouse and human sperm, both resuspended in medium, and then on human sperm incubated in CVF-containing medium; in the latter condition, the spermicidal activity and peptide stability in CVF of 17BIPHE2 were compared with that of LL-37 and GF-17. The in vivo contraceptive effects of 17BIPHE2 and the reversibility thereof were then assessed in mice. Finally, in vitro microbicidal effects of 17BIPHE2 on Neisseria gonorrhoeae were determined.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Sperm motility and plasma membrane integrity were assessed by videomicroscopy and exclusion of Sytox Green, a membrane-impermeable fluorescent dye, respectively. Successful in vitro fertilization (IVF) was determined by the presence of two pronuclei in oocytes following their coincubation with capacitated untreated or 17BIPHE2-treated sperm. Sperm alone or with 17BIPHE2 were transcervically injected into female mice and successful in vivo fertilization was indicated by the formation of two-cell embryos 42-h postinjection, and by pregnancy through pup delivery 21-25 days afterwards. Peptide intactness was assessed by immunoblotting and HPLC. Reversibility of the contraceptive effects of 17BIPHE2 was evaluated by resumption of pregnancy of the female mice, pretranscervically injected with 17BIPHE2, following natural mating with fertile males. Minimum inhibitory/bactericidal concentrations of 17BIPHE2 on N. gonorrhoeae were obtained through microdilution broth assay.
MAIN RESULTS AND THE ROLE OF CHANCE
At the same mass concentration, 17BIPHE2 was a more effective spermicide than LL-37 or GF-17 on human sperm resuspended in CVF-containing medium, with the spermicidal concentration of 32.4 µM. This was mainly due to lower susceptibility of 17BIPHE2 to CVF proteases. Importantly, the reproductive tract of mouse females treated three times with 32.4 µM 17BIPHE2 remained normal and their fecundity resumed after stopping 17BIPHE2 treatment.
LIMITATIONS, REASONS FOR CAUTION
For ethical reasons, the inhibitory effects of 17BIPHE2 on fertilization and pregnancy cannot presently be performed in women. Also, while our study has proven the effectiveness of 17BIPHE2 as a spermicide for mouse and human sperm in vitro, dosage formulation (e.g. in hydrogel) of 17BIPHE2 still needs to be developed to allow 17BIPHE2 to remain in the vagina/uterine cavity with controlled release for its spermicidal action.
WIDER IMPLICATIONS OF THE FINDINGS
Since 17BIPHE2 also exerted bactericidal activity against N. gonorrhoeae at its spermicidal concentration, it is a promising candidate to be developed into a vaginal multipurpose prevention technology agent, thus empowering women against unplanned pregnancies and sexually transmitted infections.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by the Canadian Institutes of Health Research (PJT 173268 to N.T.). There are no competing interests to declare.
TRIAL REGISTRATION NUMBER
N/A.
Topics: Pregnancy; Male; Female; Humans; Animals; Mice; Neisseria gonorrhoeae; Antimicrobial Peptides; Sperm Motility; Peptide Hydrolases; Semen; Canada; Spermatocidal Agents; Spermatozoa; Anti-Infective Agents; Contraceptive Agents; Cathelicidins
PubMed: 36053257
DOI: 10.1093/humrep/deac188 -
Annual Review of Pharmacology and... 2009Microbicides, substances applied topically to prevent sexual HIV infection, are needed to empower receptive sexual partners with effective prevention methods. Several... (Review)
Review
Microbicides, substances applied topically to prevent sexual HIV infection, are needed to empower receptive sexual partners with effective prevention methods. Several large microbicide trials, however, failed to demonstrate efficacy, thus motivating a reevaluation of the current microbicide development paradigm, which has been largely empirically based. Microbicide use occurs in a highly complex environment involving multi-level interactions, behavioral and biochemical, among host, virus, and drug, yet many details of these interactions remain unknown. Fundamental information regarding virus and drug distribution over time in sexually receptive body compartments that is necessary to design a microbicide able to outdistance and outlast the virus is largely absent. Recent efforts have been made to establish a simple conceptual framework for obtaining the knowledge that is likely to inform a more mechanistic, model-based development paradigm. These efforts have also advanced the development of numerous methodological approaches to obtain the knowledge needed to improve microbicide development.
Topics: Animals; Anti-Infective Agents, Local; Clinical Trials as Topic; HIV Infections; Humans; Models, Theoretical; Pharmacology, Clinical; Terminology as Topic
PubMed: 19006450
DOI: 10.1146/annurev.pharmtox.48.113006.094906 -
Infectious Disease Clinics of North... Dec 2014Condoms remain the most effective barrier against the sexual transmission of the human immunodeficiency virus (HIV). Male condoms have proven to be 80% to 90% effective,... (Review)
Review
Condoms remain the most effective barrier against the sexual transmission of the human immunodeficiency virus (HIV). Male condoms have proven to be 80% to 90% effective, and female condoms have similar results. Poor adherence and improper use limit their effectiveness. In addition to condoms, microbicides are a promising barrier against HIV transmission. More than 50 candidate topical microbicide compounds have undergone preclinical or clinical testing in the last 10 years, but there are currently no US Food and Drug Administration (FDA)-approved compounds. Rectal microbicides are also being developed, as anal receptive sex is an effective mode of HIV transmission.
Topics: Anti-Infective Agents, Local; Condoms; Condoms, Female; Contraception, Barrier; Female; HIV Infections; Humans; Male
PubMed: 25455315
DOI: 10.1016/j.idc.2014.08.006 -
Sexually Transmitted Diseases Jan 2007The objectives of this study were to prioritize applicator design attributes among women in the Dominican Republic and South Africa, and to determine how preferences...
OBJECTIVES
The objectives of this study were to prioritize applicator design attributes among women in the Dominican Republic and South Africa, and to determine how preferences differed based on sociodemographic variables.
GOAL
The goal was to identify acceptable microbicide applicator designs in 2 low-resource settings.
STUDY DESIGN
We surveyed 895 women, randomly sampled from clinics in the Dominican Republic (n = 449) and South Africa (n = 446), with questions on sociodemographics, applicator attribute preferences, and price/design tradeoffs.
RESULTS
Single-use design was the most valued attribute, and reusable design and low price were the least valued attributes in both populations. Preference for single-use design was associated with concern about reusable applicators spreading germs, secondary or higher education, older age, having children, and perception of moderate to high HIV risk.
CONCLUSIONS
Acceptability factors related to microbicide delivery mechanisms should continue to be evaluated among potential microbicide users to directly inform product development and introduction of microbicides.
Topics: Administration, Intravaginal; Adult; Anti-Infective Agents; Dominican Republic; Drug Delivery Systems; Female; HIV Infections; Humans; Patient Satisfaction; Sexually Transmitted Diseases; Socioeconomic Factors; South Africa; Surveys and Questionnaires; Women's Health
PubMed: 16691157
DOI: 10.1097/01.olq.0000218877.92778.fe -
Current Medicinal Chemistry 2021Vaginal drug delivery offers an opportunity for effective microbicide treatments. However, the physiological characteristics of the vagina represent a challenge when... (Review)
Review
BACKGROUND
Vaginal drug delivery offers an opportunity for effective microbicide treatments. However, the physiological characteristics of the vagina represent a challenge when preparing microbicide formulations for local delivery that avoid systemic effects.
OBJECTIVE
To review recent advances in vaginal microbicides placing special emphasis on nanocarriers that encapsulate peptide microbicides. The review includes an overview of local treatment and prevention strategies for bactericidal, fungal, protozoal and viral vaginal infections that use peptide microbicides.
METHODS
Scientific literature and clinical trials published in the PubMed database since 2015 are analyzed.
RESULT
Peptide microbicides are used for vaginal drug delivery as a means of prevention and treatment of several infectious diseases, especially sexually transmitted infections, and it is clear that such peptide-based microbicides constitute a suitable strategy. Their combination with nanotechnological drug delivery systems improves local peptide administration while avoiding their degradation and adverse effects. To date, only a few polymeric and lipid-based nanocarriers have been used for peptide microbicide vaginal delivery.
CONCLUSION
The combination of nanotechnology and peptide microbicides has emerged over recent years, and different platforms are being used for vaginal peptide delivery. Nanostructured systems for peptide delivery via vaginal rings or hydrogels are increasingly used as platforms capable of providing suitable drug delivery. However, there is still a lack of knowledge about nanocarriers aimed at encapsulating peptides for local microbicide delivery.
Topics: Administration, Intravaginal; Anti-Infective Agents; Delivery, Obstetric; Female; HIV Infections; Humans; Nanotechnology; Peptides; Pregnancy
PubMed: 33297908
DOI: 10.2174/0929867328666201209095753 -
Journal of Microbiology, Immunology,... Apr 2016Resistance of pathogenic microorganisms to antibiotics is a serious global health concern. In this review, research investigating the antimicrobial properties of honeys... (Review)
Review
Resistance of pathogenic microorganisms to antibiotics is a serious global health concern. In this review, research investigating the antimicrobial properties of honeys from around the world against skin relevant microbes is evaluated. A plethora of in vitro studies have revealed that honeys from all over the world have potent microbicidal activity against dermatologically important microbes. Moreover, in vitro studies have shown that honey can reduce microbial pathogenicity as well as reverse antimicrobial resistance. Studies investigating the antimicrobial properties of honey in vivo have been more controversial. It is evident that innovative research is required to exploit the antimicrobial properties of honey for clinical use and to determine the efficacy of honey in the treatment of a range of skin disorders with a microbiological etiology.
Topics: Anti-Infective Agents; Honey; Humans; Skin Diseases
PubMed: 25732699
DOI: 10.1016/j.jmii.2015.01.009 -
Health Care For Women International May 2017The success of women's microbicide use for HIV/AIDS prevention may hinge on health programs' ability to engage men to support it. In this qualitative study in Kenya,...
The success of women's microbicide use for HIV/AIDS prevention may hinge on health programs' ability to engage men to support it. In this qualitative study in Kenya, most women did not or would not tell their partners prior to initiating use, and/or would use despite their objections. Men generally did not agree with this, yet male partners of trial participants who discovered that their partners were using microbicides without their knowledge did not seem concerned. Findings suggest that efforts to engage men in microbicide use should avoid "awakening" patriarchal gender norms, and support women to use microbicides without involving their partners.
Topics: Administration, Intravaginal; Adult; Anti-Infective Agents; Communication; Decision Making; Disease Transmission, Infectious; Female; HIV Infections; Humans; Interviews as Topic; Kenya; Male; Patient Acceptance of Health Care; Pre-Exposure Prophylaxis; Qualitative Research; Sexual Behavior; Sexual Partners
PubMed: 28273003
DOI: 10.1080/07399332.2017.1292277