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

2014 ◽  
Vol 32 (4) ◽  
pp. 1229-1236 ◽  
Author(s):  
Bénédicte Pradines ◽  
Christian Bories ◽  
Christine Vauthier ◽  
Gilles Ponchel ◽  
Philippe M. Loiseau ◽  
...  
Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1393
Author(s):  
Monika Gosecka ◽  
Mateusz Gosecki

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.


mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Jully Pinheiro ◽  
Jacob Biboy ◽  
Waldemar Vollmer ◽  
Robert P. Hirt ◽  
Jeremy R. Keown ◽  
...  

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.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Francisco González-Salazar ◽  
Jesús N. Garza-González ◽  
Carlos E. Hernandez-Luna ◽  
Benito David Mata-Cárdenas ◽  
Pilar Carranza-Rosales ◽  
...  

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.


2018 ◽  
Author(s):  
Jully Pinheiro ◽  
Jacob Biboy ◽  
Waldemar Vollmer ◽  
Robert P. Hirt ◽  
Jeremy R. Keown ◽  
...  

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.


2019 ◽  
Vol 6 (1) ◽  
pp. 114-123
Author(s):  
Sophia Malli ◽  
Philippe M. Loiseau ◽  
Kawthar Bouchemal

Author(s):  
Ankit Kumar ◽  
Sanjeev Kumar

In case of intra-vaginal route of drug administration the dosage form is applied vaginally for the convenient release of the dosage form and for better therapeutic action of the medicament, it is usually used in HIV patients. many conditions that affect the  female reproductive tract, such as , sexually transmitted diseases, fungal & bacterial infections,  cancer and various pathogens such as virus (human immunodeficiency virus, HIV), bacteria (Gardnerella vaginalis), fungi (Candida spp.) or parasites (Trichomonas vaginalis). Systemically active drugs (contraceptive steroids) as well as locally active drugs (metronidazole Zidovudine, Lamivudine) can be effectively delivered for an extended period of time by the help of intra-vaginal  controlled release system. Continuous infusion of drugs through vaginal mucosa results in the reduced possibilities of Hepatic- gastrointestinal first-pass metabolism, gastric impatience of drugs and vacillation of dosing interval. Current study focus on the, use of various polymers which are used in hydrogels, these polymers provide bioadhesive property to the vaginal formulations, so that the vaginal formulation remains on vaginal tissues for 3- 4 days. Currently available vaginal dosage forms have several limitations, such as leakage and messiness necessitating the need to develop novel drug delivery systems.


Materials ◽  
2020 ◽  
Vol 13 (7) ◽  
pp. 1709 ◽  
Author(s):  
Guzel K. Abilova ◽  
Daulet B. Kaldybekov ◽  
Galiya S. Irmukhametova ◽  
Diara S. Kazybayeva ◽  
Zhanar A. Iskakbayeva ◽  
...  

Chitosan (CHI) and chitosan/poly(2-ethyl-2-oxazoline) (CHI/POZ)-based films were prepared by casting from aqueous solutions of polymer blends with different compositions. Ciprofloxacin was used as a model drug in these formulations. The weight, thickness, folding endurance and transparency of blend films were measured and characterised. All films had a uniform thickness (0.06 ± 0.01 mm) and exhibited sufficient flexibility. The surface pHs of films ranged from 3.76 ± 0.49 to 4.14 ± 0.32, which is within the pH range suitable for vaginal applications. The cumulative release of the drug from the films in experiments in vitro was found to be 42 ± 2% and 56 ± 1% for pure CHI and CHI/POZ (40:60) films, respectively. Drug-free chitosan/poly(2-ethyl-2-oxazoline) films showed weak antimicrobial activity against Escherichia coli. Drug-loaded CHI and CHI/POZ films showed good antimicrobial properties against both Gram-positive Staphylococcus aureus and Gram-negative bacteria Escherichia coli. Mucoadhesive properties of these films with respect to freshly excised sheep vaginal mucosa were evaluated using a tensile method. It was established that all films were mucoadhesive, but an increase in POZ content in the blend resulted in a gradual reduction of their ability to stick to vaginal mucosa. These films could potentially find applications in vaginal drug delivery.


2013 ◽  
Vol 58 (4) ◽  
Author(s):  
Brenda Escobedo-Guajardo ◽  
Francisco González-Salazar ◽  
Rebeca Palacios-Corona ◽  
Víctor Torres de la Cruz ◽  
Mario Morales-Vallarta ◽  
...  

AbstractSexually transmitted diseases are a major cause of acute disease worldwide, and trichomoniasis is the most common and curable disease, generating more than 170 million cases annually worldwide. Trichomonas vaginalis is the causal agent of trichomoniasis and has the ability to destroy in vitro cell monolayers of the vaginal mucosa, where the phospholipases A2 (PLA2) have been reported as potential virulence factors. These enzymes have been partially characterized from the subcellular fraction S30 of pathogenic T. vaginalis strains. The main objective of this study was to purify a phospholipase A2 from T. vaginalis, make a partial characterization, obtain a partial amino acid sequence, and determine its enzymatic participation as hemolytic factor causing lysis of erythrocytes. Trichomonas S30, RF30 and UFF30 sub-fractions from GT-15 strain have the capacity to hydrolyze [2-14C-PA]-PC at pH 6.0. Proteins from the UFF30 sub-fraction were separated by affinity chromatography into two eluted fractions with detectable PLA A2 activity. The EDTA-eluted fraction was analyzed by HPLC using on-line HPLC-tandem mass spectrometry and two protein peaks were observed at 8.2 and 13 kDa. Peptide sequences were identified from the proteins present in the eluted EDTA UFF30 fraction; bioinformatic analysis using Protein Link Global Server charged with T. vaginalis protein database suggests that eluted peptides correspond a putative ubiquitin protein in the 8.2 kDa fraction and a phospholipase preserved in the 13 kDa fraction. The EDTA-eluted fraction hydrolyzed [2-14C-PA]-PC lyses erythrocytes from Sprague-Dawley in a time and dose-dependent manner. The acidic hemolytic activity decreased by 84% with the addition of 100 μM of Rosenthal’s inhibitor.


Planta Medica ◽  
2021 ◽  
Author(s):  
Nathalya Tesch Brazil ◽  
Bruna Medeiros-Neves ◽  
Flávia Nathiely Silveira Fachel ◽  
Vanessa Pittol ◽  
Roselena Silvestri Schuh ◽  
...  

Abstract Trichomonas vaginalis causes trichomoniasis, a nonviral sexually transmitted infection with a high prevalence worldwide. Oral metronidazole is the drug of choice for the treatment of this disease, although high levels of T. vaginalis resistance to this agent are well documented in the literature. This study describes the anti-T. vaginalis activity of an optimized coumarin-rich extract from Pterocaulon balansae. Optimization was performed to maximize extraction of total coumarins by means of a 3-level Box-Behnken design, evaluating the effect of three factors: extraction time, plant : solvent ratio, and ethanol concentration. Optimum conditions were found to be 5 h extraction time and a plant : solvent ratio of 1% (w/v) and 60% (v/v) ethanol, which resulted in approximately 30 mg of total coumarins/g of dry plant. The coumarin-enriched extract exhibited a minimum inhibitory concentration of 30 µg/mL and an IC50 of 3.2 µg/mL against T. vaginalis, a low cytotoxicity, and a high selectivity index (18 for vaginal epithelial cells and 16 for erythrocytes). The coumarins permeation/retention profile through porcine vaginal mucosa was evaluated in Franz-type diffusion cells. After 8 h of kinetics, coumarins were detected in the tissue (4.93 µg/g) without detecting them in the receptor compartment. A significant increase of coumarins in the mucosa layers (8.18 µg/g) and receptor compartment (0.26 µg/g) was detected when a T. vaginalis suspension (2 × 105 trophozoites/mL) was previously added onto the mucosa. No alterations were visualized in the stratified squamous non-keratinized epithelium of the porcine vaginal mucosa after contact with the extract. Overall, these results suggest that the P. balansae coumarin-rich extract may have potential as a treatment for trichomoniasis.


Author(s):  
A. Campos ◽  
J. Vilches ◽  
J. Gomez

Microgranules have been described with different names in keratinized and in nonkeratinized epithelium. In keratinized epithelium it seems clear that the microgranules are lamellated bodies bounded by a membrane which empty their contents into the intercellular space. Their existence in nonkeratinized epithelium is more debatable. Until now the so-called microgranules have been described in nonkeratinized bucal, lingual and cervical epithelium. In the present work we describe the morphology and nature of such structures in human vaginal epithelium.Biopsies from the midlevel of the vaginal mucosa were taken from voluntary fertile women. The specimens were divided into three groups with four vaginal specimens. The first group was obtained in the folicular phase; those of the second in the postovulatory phase and, finally, the last group corresponded to the secretory phase.


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