Antimicrobial Polymer-Based Hydrogels for the Intravaginal Therapies—Engineering Considerations

The review is focused on the hydrogel systems dedicated to the intravaginal delivery of antibacterial, antifungal and anti-Trichomonas vaginalis activity drugs for the treatment of gynaecological infections. The strategies for the enhancement of the hydrophobic drug solubility in the hydrogel matrix based on the formation of bigel systems and the introduction of nano- and microparticles as a drug reservoir are presented. Hydrogel carriers of natural and synthetic pharmacological substances, drug-free systems displaying antimicrobial activity thanks to the hydrogel building elements and systems combining the antimicrobial activity of both drug and polymer building components are distinguished. The design of hydrogels facilitating their administration and proper distribution in the vaginal mucosa and the vagina based on thermoresponsive systems capable of gelling at vaginal conditions and already-cross-linked injectable systems after reaching the yield stress are discussed. In addition, the mechanisms of hydrogel bioadhesion that regulate the retention time in the vagina are indicated. Finally, the prospects for the further development of hydrogel-based drug carriers in gynaecological therapies are highlighted.

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Drug-Free Chitosan Coated Poly(isobutylcyanoacrylate) Nanoparticles Are Active Against Trichomonas vaginalis and Non-Toxic Towards Pig Vaginal Mucosa

Pharmaceutical Research ◽

10.1007/s11095-014-1528-7 ◽

2014 ◽

Vol 32 (4) ◽

pp. 1229-1236 ◽

Cited By ~ 20

Author(s):

Bénédicte Pradines ◽

Christian Bories ◽

Christine Vauthier ◽

Gilles Ponchel ◽

Philippe M. Loiseau ◽

...

Keyword(s):

Trichomonas Vaginalis ◽

Vaginal Mucosa ◽

Drug Free

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Design and synthesis of thiamine analogues to study their binding to the ECF transporter for thiamine in bacteria

MedChemComm ◽

10.1039/c6md00022c ◽

2016 ◽

Vol 7 (5) ◽

pp. 966-971 ◽

Cited By ~ 5

Author(s):

L. Monjas ◽

L. J. Y. M. Swier ◽

A. R. de Voogd ◽

R. C. Oudshoorn ◽

A. K. H. Hirsch ◽

...

Keyword(s):

Antimicrobial Activity ◽

Substrate Specificity ◽

Small Molecules ◽

Energy Coupling ◽

Coupling Factor ◽

Design And Synthesis ◽

Further Development ◽

Thiamine Analogues

This work presents new small molecules that bind to the protein ThiT, which confers substrate specificity to the Energy-Coupling Factor (ECF) transporter for thiamine. Further development of the molecules may lead to compounds with antimicrobial activity.

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Antimicrobial activity, total phenolic content and flavonoid concentrations of Teucrium species

Open Life Sciences ◽

10.2478/s11535-012-0048-x ◽

2012 ◽

Vol 7 (4) ◽

pp. 664-671 ◽

Cited By ~ 4

Author(s):

Milan Stanković ◽

Olgica Stefanović ◽

Ljiljana Čomić ◽

Marina Topuzović ◽

Ivana Radojević ◽

...

Keyword(s):

Antimicrobial Activity ◽

Total Phenolic Content ◽

Antimicrobial Agents ◽

Phenolic Content ◽

Fungal Species ◽

Total Phenolic ◽

Total Phenols ◽

Further Development ◽

Ethyl Acetate Extracts

AbstractIn vitro antimicrobial activity of 21 crude extracts obtained from seven taxa of the genus Teucrium (T. chamaedrys, T. montanum, T. arduini, T. polium, T. scordium subsp. scordium, T. scordium subsp. scordioides and T. botrys) was tested against bacterial and fungal species. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined using a microdilution analysis method. Total phenolic content and flavonoid concentrations were measured spectrophotometrically. Total phenols were determined using Folin-Ciocalteu reagent and their amounts ranged from 28.49 up to 159.84 mg CA/g of extract (chlorogenic acid equivalent). The amounts of flavonoids ranged from 38.17 up to 190.45 mg RU/g of extract (rutin equivalent).The plant extracts showed greater potential of antibacterial than antifungal activity. A relationship was found between total phenolics and biological activity. The highest level of total phenols was measured in the methanol extracts, which demonstrated higher antimicrobial activity than acetone and ethyl acetate extracts. Staphylococcus aureus ATCC 25923 appeared to be the most sensitive organism. Our results indicate that Teucrium spp extracts are rich sources of phenolic compounds and are promising candidates for further development as natural antimicrobial agents.

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Neomycin Sulfate Improves the Antimicrobial Activity of Mupirocin-Based Antibacterial Ointments

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02083-15 ◽

2015 ◽

Vol 60 (2) ◽

pp. 862-872 ◽

Cited By ~ 11

Author(s):

Catlyn Blanchard ◽

Lauren Brooks ◽

Andrew Beckley ◽

Jennifer Colquhoun ◽

Stephen Dewhurst ◽

...

Keyword(s):

Antimicrobial Activity ◽

Invasive Disease ◽

Wound Site ◽

Content Type ◽

Neomycin Sulfate ◽

Resistant Strains ◽

Mupirocin Ointment ◽

High Level ◽

Further Development ◽

New Strategies

ABSTRACTIn the midst of the current antimicrobial pipeline void, alternative approaches are needed to reduce the incidence of infection and decrease reliance on last-resort antibiotics for the therapeutic intervention of bacterial pathogens. In that regard, mupirocin ointment-based decolonization and wound maintenance practices have proven effective in reducingStaphylococcus aureustransmission and mitigating invasive disease. However, the emergence of mupirocin-resistant strains has compromised the agent's efficacy, necessitating new strategies for the prevention of staphylococcal infections. Herein, we set out to improve the performance of mupirocin-based ointments. A screen of a Food and Drug Administration (FDA)-approved drug library revealed that the antibiotic neomycin sulfate potentiates the antimicrobial activity of mupirocin, whereas other library antibiotics did not. Preliminary mechanism of action studies indicate that neomycin's potentiating activity may be mediated by inhibition of the organism's RNase P function, an enzyme that is believed to participate in the tRNA processing pathway immediately upstream of the primary target of mupirocin. The improved antimicrobial activity of neomycin and mupirocin was maintained in ointment formulations and reducedS. aureusbacterial burden in murine models of nasal colonization and wound site infections. Combination therapy improved upon the effects of either agent alone and was effective in the treatment of contemporary methicillin-susceptible, methicillin-resistant, and high-level mupirocin-resistantS. aureusstrains. From these perspectives, combination mupirocin-and-neomycin ointments appear to be superior to that of mupirocin alone and warrant further development.

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Evaluation of Antimicrobial Activity of Trachyspermum ammi (L.) Sprague Essential Oil and Its Active Constituent, Thymol, against Vaginal Pathogens

Traditional and Integrative Medicine ◽

10.18502/tim.v5i2.3625 ◽

2020 ◽

Author(s):

Mozhgan MehriArdestani ◽

Atousa Aliahmadi ◽

Tayebeh Toliat ◽

Abdolhossein Dalimi ◽

Zohreh Momeni ◽

...

Keyword(s):

Antimicrobial Activity ◽

Essential Oil ◽

Trichomonas Vaginalis ◽

Antimicrobial Agents ◽

Gardnerella Vaginalis ◽

Active Constituent ◽

Candida Spp ◽

Vaginal Infections ◽

Trachyspermum Ammi ◽

Conventional Antibiotics

Vaginal infections are one of the major reasons women visit a gynecologist. Increased resistance to conventional antibiotics is one of the main factors mitigating the development of new antimicrobial agents, especially those of natural origin. In traditional Persian medicine, Trachyspermum ammi has been claimed to clear vagina from excessive discharge. Therefore, in this study, the antimicrobial activity of Ajwain essential oil was evaluated against some vaginal pathogens. The essential oil of ajwain was picked up and the minimum inhibitory and bactericidal concentrations (MIC and MBC) were revealed. The most frequently detected microorganisms involved in genital infections including Candida spp., Gardnerella vaginalis, Escherichia coli, Staphylococcus aureus, Streptococcus agalactiae and Lactobacillus acidophilus were considered. Evaluation of the essential oil of Trichomonas vaginalis was done by calculation of percent of growth inhibition. The essential oil showed a remarkable activity against the studied bacteria and fungi with MIC at a range of 0.0315 - 0.5 mg/ml and MBC at a range of 0.125 - 4 mg /ml. The highest inhibition and bactericidal activity was observed in S. agalactiae and G. vaginalis. 100% inhibition of T. vaginalis growth was shown at a concentration of 2000 μg/ml after 48 h by essential oil. The antimicrobial activity of the essential oil was more than that of thymol. Supposedly essential oil of Trachyspermum ammi fruit could inhibit vaginal pathogens growth .Further preclinical and clinical studies are required to confirm the efficacy of this natural agent in vaginitis.

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The ProtozoanTrichomonas vaginalisTargets Bacteria with Laterally Acquired NlpC/P60 Peptidoglycan Hydrolases

mBio ◽

10.1128/mbio.01784-18 ◽

2018 ◽

Vol 9 (6) ◽

Cited By ~ 5

Author(s):

Jully Pinheiro ◽

Jacob Biboy ◽

Waldemar Vollmer ◽

Robert P. Hirt ◽

Jeremy R. Keown ◽

...

Keyword(s):

Trichomonas Vaginalis ◽

Close Association ◽

Transmitted Disease ◽

Mixed Cultures ◽

Vaginal Mucosa ◽

Transmitted Infection ◽

Content Type ◽

Sexually Transmitted ◽

Study Results ◽

Peptidoglycan Hydrolases

ABSTRACTThe human eukaryotic pathogenTrichomonas vaginaliscauses trichomoniasis, a prevalent sexually transmitted infection. This extracellular protozoan is intimately associated with the human vaginal mucosa and microbiota, but key aspects of the complex interactions between the parasite and the vaginal bacteria remain elusive. We report thatT. vaginalishas acquired, by lateral gene transfer from bacteria, genes encoding peptidoglycan hydrolases of the NlpC/P60 family. Two of theT. vaginalisenzymes were active against bacterial peptidoglycan, retaining the active-site fold and specificity asdl-endopeptidases. The endogenous NlpC/P60 genes are transcriptionally upregulated inT. vaginalisin the presence of bacteria. The overexpression of an exogenous copy enables the parasite to outcompete bacteria from mixed cultures, consistent with the biochemical activity of the enzyme. Our study results highlight the relevance of the interactions of this eukaryotic pathogen with bacteria, a poorly understood aspect of the biology of this important human parasite.IMPORTANCETrichomonas vaginalisis a parasitic protozoan of the human urogenital tract that causes trichomoniasis, a very common sexually transmitted disease. Despite residing extracellularly and in close association with the vaginal bacteria (i.e., the microbiota), very little is known about the nature of the parasite-bacterium interactions. Our study showed that this parasite had acquired genes from bacteria which retained their original function. They produce active enzymes capable of degrading peptidoglycan, a unique polymer of the bacterial cell envelope, helping the parasite to outcompete bacteria in mixed cultures. This study was the first to show that a laterally acquired group of genes enables a eukaryotic mucosal pathogen to control bacterial population. We highlight the importance of understanding the interactions between pathogens and microbiota, as the outcomes of these interactions are increasingly understood to have important implications on health and disease.

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Sphingomyelinase Activity ofTrichomonas vaginalisExtract and Subfractions

BioMed Research International ◽

10.1155/2013/679365 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Francisco González-Salazar ◽

Jesús N. Garza-González ◽

Carlos E. Hernandez-Luna ◽

Benito David Mata-Cárdenas ◽

Pilar Carranza-Rosales ◽

...

Keyword(s):

Trichomonas Vaginalis ◽

Inflammatory Responses ◽

Vaginal Mucosa ◽

Total Extract ◽

Sexually Transmitted ◽

Cell Monolayers ◽

Type C ◽

Induced Apoptosis ◽

Two Peaks

Trichomoniasis is one of the most common acute sexually transmitted curable diseases, and it is disseminated worldwide generating more than 170 million cases annually.Trichomonas vaginalisis the parasite that causes trichomoniasis and has the ability to destroy cell monolayers of the vaginal mucosain vitro. Sphingomyelinases (SMase) are enzymes that catalyze the hydrolysis of sphingomyelin into ceramide and phosphorylcholine. Ceramide appears to be a second messenger lipid in programmed apoptosis, cell differentiation, and cell proliferation. Sphingomyelinase is probably a major source of ceramide in cells. Signal transduction mediated by ceramide leads cells to produce cytokine induced apoptosis during several inflammatory responses. SMase are also relevant toxins in several microorganisms. The main objective of this research is to identify SMase activity ofT. vaginalisin the total extract (TE), P30, and S30 subfractions from brooked trophozoites. It was found that these fractions ofT. vaginalishave SMase activity, which comes principally from P30 subfraction and was mainly type C. Enzymatic activity of SMase increased linearly with time and is pH dependent with two peaks by pH 5.5 and pH 7.5. The addition of manganese to the reaction mixture increased the SMase activity by 1.97.

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The protozoanTrichomonas vaginalistargets bacteria with laterally-acquired NlpC/P60 peptidoglycan hydrolases

10.1101/320382 ◽

2018 ◽

Author(s):

Jully Pinheiro ◽

Jacob Biboy ◽

Waldemar Vollmer ◽

Robert P. Hirt ◽

Jeremy R. Keown ◽

...

Keyword(s):

Trichomonas Vaginalis ◽

Close Association ◽

Transmitted Disease ◽

Protozoan Parasite ◽

Mixed Cultures ◽

Vaginal Mucosa ◽

Transmitted Infection ◽

Sexually Transmitted ◽

Peptidoglycan Hydrolases

AbstractTrichomonas vaginalisis a human eukaryotic pathogen and the causative agent of trichomoniasis, the most prevalent non-viral sexually transmitted infection worldwide. This extracellular protozoan parasite is intimately associated with the human vaginal mucosa and microbiota but key aspects of the complex interactions between the parasite and the vaginal bacteria remain elusive. We report thatT. vaginalishas acquired, by lateral gene transfer from bacteria, genes encoding peptidoglycan hydrolases of the NlpC/P60 family. Two of theT. vaginalisenzymes were active against bacterial peptidoglycan, retaining the active site fold and specificity as DL-endopeptidases. The endogenous NlpC/P60 genes are transcriptionally up regulated inT. vaginaliswhen in the presence of bacteria. The over-expression of an exogenous copy produces a remarkable phenotype where the parasite is capable of competing out bacteria from mixed cultures, consistent with the biochemical activity of the enzymein vitro. Our study highlights the relevance of the interactions of this eukaryotic pathogen with bacteria, a poorly understood aspect on the biology of this important human parasite.Author summaryTrichomonas vaginalisis a protozoan parasite that causes a very common sexually transmitted disease known as trichomoniasis. This extracellular parasite resides in the vagina where it is in close association with the mucosa and the local microbiota. Very little is known about the nature of the parasite-bacteria interactions. Here, we report that this parasite had acquired genes from bacteria which retained their original function producing active enzymes capable of degrading peptidoglycan, a polymer that is chemically unique to the cell envelope of bacteria. Our results indicate that these enzymes help the parasite compete out bacteria in mixed cultures. These observations suggest that these enzymes may be critical for the parasite to establish infection in the vagina, a body site that is densely colonised with bacteria. Our study further highlights the importance of understanding the interactions between pathogens and microbiota, as the outcomes of these interactions are increasingly understood to have important implications on health and disease.

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