scholarly journals Development andIn VivoEvaluation of a Novel Histatin-5 Bioadhesive Hydrogel Formulation against Oral Candidiasis

2015 ◽  
Vol 60 (2) ◽  
pp. 881-889 ◽  
Author(s):  
Eric F. Kong ◽  
Christina Tsui ◽  
Heather Boyce ◽  
Ahmed Ibrahim ◽  
Stephen W. Hoag ◽  
...  
Keyword(s):  
Oral Candidiasis ◽  
Hydroxypropyl Methylcellulose ◽  
Antimicrobial Properties ◽  
Content Type ◽  
Histatin 5 ◽  
Common Opportunistic Infection ◽  
Hydrogel Formulation ◽  
New Formulation

ABSTRACTOral candidiasis (OC), caused by the fungal pathogenCandida albicans, is the most common opportunistic infection in HIV+individuals and other immunocompromised populations. The dramatic increase in resistance to common antifungals has emphasized the importance of identifying unconventional therapeutic options. Antimicrobial peptides have emerged as promising candidates for therapeutic intervention due to their broad antimicrobial properties and lack of toxicity. Histatin-5 (Hst-5) specifically has exhibited potent anticandidal activity indicating its potential as an antifungal agent. To that end, the goal of this study was to design a biocompatible hydrogel delivery system for Hst-5 application. The bioadhesive hydroxypropyl methylcellulose (HPMC) hydrogel formulation was developed for topical oral application against OC. The new formulation was evaluatedin vitrofor gel viscosity, Hst-5 release rate from the gel, and killing potency and, more importantly, was testedin vivoin our mouse model of OC. The findings demonstrated a controlled sustained release of Hst-5 from the polymer and rapid killing ability. Based on viableC. albicanscounts recovered from tongues of treated and untreated mice, three daily applications of the formulation beginning 1 day postinfection withC. albicanswere effective in protection against development of OC. Interestingly, in some cases, Hst-5 was able to clear existing lesions as well as associated tissue inflammation. These findings were confirmed by histopathology analysis of tongue tissue. Coupled with the lack of toxicity as well as anti-inflammatory and wound-healing properties of Hst-5, the findings from this study support the progression and commercial feasibility of using this compound as a novel therapeutic agent.

scholarly journals Histatin 5-Spermidine Conjugates Have Enhanced Fungicidal Activity and Efficacy as a Topical Therapeutic for Oral Candidiasis

2013 ◽  
Vol 58 (2) ◽  
pp. 756-766 ◽  
Author(s):  
Swetha Tati ◽  
Rui Li ◽  
Sumant Puri ◽  
Rohitashw Kumar ◽  
Peter Davidow ◽  
...  
Keyword(s):  
Fungicidal Activity ◽  
Oral Candidiasis ◽  
Therapeutic Agents ◽  
Commensal Bacteria ◽  
Biofilm Growth ◽  
Opportunistic Fungi ◽  
Content Type ◽  
Histatin 5 ◽  
Immunocompromised Mice

ABSTRACTOropharyngeal candidiasis (OPC) is caused by the opportunistic fungiCandida albicansand is prevalent in immunocompromised patients, individuals with dry mouth, or patients with prolonged antibiotic therapies that reduce oral commensal bacteria. Human salivary histatins, including histatin 5 (Hst 5), are small cationic proteins that are the major source of fungicidal activity of saliva. However, Hsts are rapidly degradedin vivo, limiting their usefulness as therapeutic agents despite their lack of toxicity. We constructed a conjugate peptide using spermidine (Spd) linked to the active fragment of Hst 5 (Hst 54–15), based upon our findings thatC. albicansspermidine transporters are required for Hst 5 uptake and fungicidal activity. We found that Hst 54–15-Spd was significantly more effective in killingC. albicansandCandida glabratathan Hst 5 alone in both planktonic and biofilm growth and that Hst 54–15-Spd retained high activity in both serum and saliva. Hst 54–15-Spd was not bactericidal against streptococcal oral commensal bacteria and had no hemolytic activity. We tested the effectiveness of Hst 54–15-Spdin vivoby topical application to tongue surfaces of immunocompromised mice with OPC. Mice treated with Hst 54–15-Spd had significant clearance of candidal tongue lesions macroscopically, which was confirmed by a 3- to 5-log fold reduction ofC. albicanscolonies recovered from tongue tissues. Hst 54–15-Spd conjugates are a new class of peptide-based drugs with high selectivity for fungi and potential as topical therapeutic agents for oral candidiasis.

Bioactive peptides from egg: a review

2015 ◽  
Vol 45 (2) ◽  
pp. 190-212 ◽  
Author(s):  
Z. F. Bhat ◽  
Sunil Kumar ◽  
Hina Fayaz Bhat
Keyword(s):  
Bioactive Peptides ◽  
Antioxidant Activities ◽  
Positive Impact ◽  
Antimicrobial Properties ◽  
Specific Protein ◽  
Biologically Active ◽  
Content Type ◽  
Treatment And Prevention

Purpose – The aim of the article was to focus on various peptides identified in the egg and their probable application as novel ingredients in the development of functional food products. Bioactive peptides of egg origin have attracted increasing interest as one of the prominent candidates for development of various health-promoting functional and designer foods. Design/methodology/approach – Traditionally known as a source of highly valuable proteins in human nutrition, eggs are nowadays also considered as an important source of many bioactive peptides which may find wide application in medicine and food production. These specific protein fragments from egg proteins which, above and beyond their nutritional capabilities, have a positive impact on the body’s function or condition by affecting the digestive, endocrine, cardiovascular, immune and nervous systems, and may ultimately influence health. Findings – Several peptides that are released in vitro or in vivo from egg proteins have been attributed to different health effects, including antihypertensive effects, antimicrobial properties, antioxidant activities, anticancer activity, immunomodulating activity, antiadhesive properties and enhancement of nutrient absorption and/or bioavailability. Extensive research has been undertaken to identify and characterize these biologically active peptides of egg origin which has changed the image of egg as a new source of biologically active ingredients for the development of functional foods with specific benefits for human health and treatment and prevention of diseases. Originality/value – The paper mainly describes the above-stated properties of bioactive peptides derived from egg proteins.

scholarly journals Anthocyanin as potential source for antimicrobial activity inClitoria ternateaL. andDioscorea alataL.

2018 ◽  
Vol 47 (6) ◽  
pp. 490-495 ◽  
Author(s):  
Noraini Mahmad ◽  
R.M. Taha ◽  
Rashidi Othman ◽  
Sakinah Abdullah ◽  
Nordiyanah Anuar ◽  
...  
Keyword(s):  
Antimicrobial Properties ◽  
Blue Flower ◽  
Distilled Water ◽  
Content Type ◽  
E Coli ◽  
Inhibition Zones ◽  
Antibacterial And Antifungal ◽  
Purple Yam

PurposeThe purpose of this paper is to validate the antimicrobial activity (both antibacterial and antifungal) ofin vivoandin vitroethanolic anthocyanin extracts ofClitoria ternateaL. (vivid blue flower butterfly-pea) andDioscorea alataL. (purple yam) against selected bacteria (Bacillus subtilis,Staphylococcus aureusandEscherichia coli) and fungi (Fusarium sp.,Aspergillus nigerandTrichoderma sp.).Design/methodology/approachThe freeze-dried samples (0.2 g) fromin vivovivid blue flowers ofC. ternateaL. were extracted using 10 mL ethanol (produced ethanolic red extraction) and 10 mL distilled water (produced aqueous blue extraction) separately. Two-month-oldin vitrocallus samples (0.2 g) were only extracted using 10 mL ethanol. The anthocyanin extractions were separated with the addition (several times) of ethyl acetate and distilled water (1:2:3) to remove stilbenoids, chlorophyll, less polar flavonoids and other non-polar compounds. Furthermore, the antimicrobial properties were determined using agar diffusion technique. Three bacteria (B. subtilis,S. aureusandE. coli) and fungi (F. sp.,A. nigerandT. sp.) were streaked on bacteria agar and dextrose agar, respectively, using “hockey stick”. Then, the sterile paper discs (6 mm diameter) were pipetted with 20 µL of 1,010 CFU/mL chloramphenicol (as control for antibacterial) and carbendazim (as control for antifungal)in vivoandin vitroextracts. The plates were incubated at room temperature for 48 h, and the inhibition zones were measured.FindingsBased on the results, bothin vivoandin vitroethanolic extracts from vivid blue flowers ofC. ternateaL. showed the best antibacterial activity against the same bacteria (B. subtilis), 11 and 10 mm inhibition zones, respectively. However, different antifungal activity was detected inin vitroethanolic callus extract (12 mm), which was againstT. sp., contrary toin vivoethanolic extract (10 mm), which was againstF. sp.; antibacterial activity ofD. alataL. was seen against the same bacteria (E. coli) with the highest inhibition zone forin vivoextract (8.8 mm), followed byin vitroextract (7.8 mm).Research limitations/implicationsAnthocyanins are responsible for the water soluble and vacuolar, pink, red, purple and blue pigments present in coloured plant pigments. These pigments (pink, red, purple and blue) are of important agronomic value in many crops and ornamental plants. However, anthocyanins are not stable and are easy to degrade and fade whenever exposed to light.Social implicationsPlant extracts containing bioactive agents with antimicrobial properties have been found to be useful in treating bacterial and fungal infections, as well as showed multiple antibiotic resistance.Originality/valueBothin vivoandin vitroextracts from vivid blue flower petals (C. ternateaL.) and purple yam (D. alataL.) have important applications as natural antimicrobial (antibacterial and antifungal) agents in the coating industry, instead of natural pharmaceutical products.

scholarly journals In VitroActivity of Miltefosine against Candida albicans under Planktonic and Biofilm Growth Conditions andIn VivoEfficacy in a Murine Model of Oral Candidiasis

2015 ◽  
Vol 59 (12) ◽  
pp. 7611-7620 ◽  
Author(s):  
Taissa Vieira Machado Vila ◽  
Ashok K. Chaturvedi ◽  
Sonia Rozental ◽  
Jose L. Lopez-Ribot
Keyword(s):  
Candida Albicans ◽  
Murine Model ◽  
Biofilm Formation ◽  
Pathogenic Fungus ◽  
Oral Candidiasis ◽  
Antifungal Drugs ◽  
Drug Candidate ◽  
Content Type

ABSTRACTThe generation of a new antifungal againstCandida albicansbiofilms has become a major priority, since biofilm formation by this opportunistic pathogenic fungus is usually associated with an increased resistance to azole antifungal drugs and treatment failures. Miltefosine is an alkyl phospholipid with promising antifungal activity. Here, we report that, when tested under planktonic conditions, miltefosine displays potentin vitroactivity against multiple fluconazole-susceptible and -resistantC. albicansclinical isolates, including isolates overexpressing efflux pumps and/or with well-characterized Erg11 mutations. Moreover, miltefosine inhibitsC. albicans biofilm formation and displays activity against preformed biofilms. Serial passage experiments confirmed that miltefosine has a reduced potential to elicit resistance, and screening of a library ofC. albicanstranscription factor mutants provided additional insight into the activity of miltefosine againstC. albicansgrowing under planktonic and biofilm conditions. Finally, we demonstrate thein vivoefficacy of topical treatment with miltefosine in the murine model of oropharyngeal candidiasis. Overall, our results confirm the potential of miltefosine as a promising antifungal drug candidate, in particular for the treatment of azole-resistant and biofilm-associated superficial candidiasis.

scholarly journals Synergistic Combination of Chitosan Acetate with Nanoparticle Silver as a Topical Antimicrobial: Efficacy against Bacterial Burn Infections

2011 ◽  
Vol 55 (7) ◽  
pp. 3432-3438 ◽  
Author(s):  
Liyi Huang ◽  
Tianhong Dai ◽  
Yi Xuan ◽  
George P. Tegos ◽  
Michael R. Hamblin
Keyword(s):  
Survival Rates ◽  
Antimicrobial Properties ◽  
Silver Ions ◽  
Antimicrobial Efficacy ◽  
Bacterial Cells ◽  
Content Type ◽  
Freeze Dried ◽  
Topical Antimicrobial

ABSTRACTChitosan and nanoparticle silver are both materials with demonstrated antimicrobial properties and have been proposed singly or in combination as constituents of antimicrobial burn dressings. Here, we show that they combine synergistically to inhibit thein vitrogrowth of Gram-positive methicillin-resistantStaphylococcus aureus(MRSA) and Gram-negative bacteria (Pseudomonas aeruginosa,Proteus mirabilis, andAcinetobacter baumannii), as judged by bioluminescence monitoring and isobolographic analysis, and also produce synergistic killing after 30 min of incubation, as measured by a CFU assay. The hypothesized explanation involves chitosan-mediated permeabilization of bacterial cells, allowing better penetration of silver ions into the cell. A dressing composed of freeze-dried chitosan acetate incorporating nanoparticle silver was compared with a dressing of chitosan acetate alone in anin vivoburn model infected with bioluminescentP. aeruginosa. The survival rates of mice treated with silver-chitosan or regular chitosan or left untreated were 64.3% (P= 0.0082 versus regular chitosan andP= 0.0003 versus the control), 21.4%, and 0%, respectively. Most of the fatalities occurred between 2 and 5 days postinfection. Silver-chitosan dressings effectively controlled the development of systemic sepsis, as shown by blood culture. These data suggest that a dressing combining chitosan acetate with silver leads to improved antimicrobial efficacy against fatal burn infections.

scholarly journals Antifungal Activity of Oleylphosphocholine on In Vitro and In Vivo Candida albicans Biofilms

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Michelle Holtappels ◽  
Erwin Swinnen ◽  
Lies De Groef ◽  
Jurgen Wuyts ◽  
Lieve Moons ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Biofilm Formation ◽  
Ex Vivo ◽  
Oral Candidiasis ◽  
Sprague Dawley ◽  
Content Type ◽  
Polyurethane Catheters

ABSTRACT In this study, we investigated the potential antifungal activity of the alkylphospholipid oleylphosphocholine (OlPC), a structural analogue of miltefosine, on in vitro and in vivo Candida albicans biofilm formation. The effect of OlPC on in vitro and in vivo C. albicans biofilms inside triple-lumen polyurethane catheters was studied. In vivo biofilms were developed subcutaneously after catheter implantation on the lower back of Sprague-Dawley rats. Animals were treated orally with OlPC (20 mg/kg of body weight/day) for 7 days. The effect of OlPC on biofilms that developed on the mucosal surface was studied in an ex vivo model of oral candidiasis. The role of OlPC in C. albicans morphogenesis was investigated by using hypha-inducing media, namely, Lee, Spider, and RPMI 1640 media. OlPC displayed activity against both planktonic cells and in vitro C. albicans biofilms. To completely abolish preformed, 24-h-old biofilms, higher concentrations (8, 10, and 13 mg/liter) were needed. Moreover, OlPC was able to reduce C. albicans biofilms formed by caspofungin-resistant clinical isolates and acted synergistically when combined with caspofungin. The daily oral administration of OlPC significantly reduced in vivo C. albicans biofilms that developed subcutaneously. In addition, OlPC decreased biofilm formation on mucosal surfaces. Interestingly, the application of subinhibitory concentrations of OlPC already inhibited the yeast-to-hypha transition, a crucial virulence factor of C. albicans. We document, for the first time, the effects of OlPC on C. albicans cells and suggest the potential use of OlPC for the treatment of C. albicans biofilm-associated infections.

Preparation and Evaluation of Gemifloxacin Mesylate Floating Matrix Tablets in Healthy Human Volunteers

2017 ◽  
Vol 10 (1) ◽  
pp. 3623-3630
Author(s):  
Bhikshapathi D. V. R. N. ◽  
Haarika B ◽  
Jyothi Sri S ◽  
K Abbulu
Keyword(s):  
Drug Release ◽  
Sodium Bicarbonate ◽  
Polymer Concentration ◽  
Hydroxypropyl Methylcellulose ◽  
Matrix Tablets ◽  
Physical Parameters ◽  
Drug Bioavailability ◽  
Floating Tablets

The purpose of present investigation was to develop floating matrix tablets of gemifloxacin mesylate, which after oral administration could prolong the gastric residence time, increase the drug bioavailability and diminish the side effects of irritating drugs. Tablets containing drug, various viscosity grades of hydroxypropyl methylcellulose such as HPMC K4M and HPMC K15M as matrix forming agent, Sodium bicarbonate as gas-forming agent and different additives were tested for their usefulness in formulating gastric floating tablets by direct compression method. The physical parameters, in vitro buoyancy, release characteristics and in vivo radiographic study were investigated in this study. The gemifloxacin mesylate floating tablets were prepared using HPMC K4M polymer giving more sustained drug release than the tablet containing HPMC K15M. All these formulations showed floating lag time of 30 to 47 sec and total floating time more than 12 h. The drug release was decreased when polymer concentration increases and gas generating agent decreases. Formulation that contains maximum concen-tration of both HPMC K15M and sodium bicarbonate (F9) showing sufficiently sustained with 99.2% of drug release at 12 h. The drug release from optimized formulation follows Higuchi model that indicates the diffusion controlled release. The best formulation (F9) was selected based on in vitro characteristics and used in vivo radiographic studies by incorporating barium sulphate as a radio-opaque agent and the tablet remained in the stomach for about 6 h.   

scholarly journals Antimicrobial Activity of Curcumin in Nanoformulations: A Comprehensive Review

2021 ◽  
Vol 22 (13) ◽  
pp. 7130
Author(s):  
Jeffersson Krishan Trigo-Gutierrez ◽  
Yuliana Vega-Chacón ◽  
Amanda Brandão Soares ◽  
Ewerton Garcia de Oliveira Mima
Keyword(s):  
Polymeric Nanoparticles ◽  
Graphene Quantum Dots ◽  
Antimicrobial Properties ◽  
Antimicrobial Effect ◽  
Clinical Scenarios ◽  
Low Cytotoxicity ◽  
Bacteria And Fungi ◽  
Drug Resistant Strains

Curcumin (CUR) is a natural substance extracted from turmeric that has antimicrobial properties. Due to its ability to absorb light in the blue spectrum, CUR is also used as a photosensitizer (PS) in antimicrobial Photodynamic Therapy (aPDT). However, CUR is hydrophobic, unstable in solutions, and has low bioavailability, which hinders its clinical use. To circumvent these drawbacks, drug delivery systems (DDSs) have been used. In this review, we summarize the DDSs used to carry CUR and their antimicrobial effect against viruses, bacteria, and fungi, including drug-resistant strains and emergent pathogens such as SARS-CoV-2. The reviewed DDSs include colloidal (micelles, liposomes, nanoemulsions, cyclodextrins, chitosan, and other polymeric nanoparticles), metallic, and mesoporous particles, as well as graphene, quantum dots, and hybrid nanosystems such as films and hydrogels. Free (non-encapsulated) CUR and CUR loaded in DDSs have a broad-spectrum antimicrobial action when used alone or as a PS in aPDT. They also show low cytotoxicity, in vivo biocompatibility, and improved wound healing. Although there are several in vitro and some in vivo investigations describing the nanotechnological aspects and the potential antimicrobial application of CUR-loaded DDSs, clinical trials are not reported and further studies should translate this evidence to the clinical scenarios of infections.

scholarly journals Exogenous Alginate Protects Staphylococcus aureus from Killing by Pseudomonas aeruginosa

2019 ◽  
Vol 202 (8) ◽  
Author(s):  
Courtney E. Price ◽  
Dustin G. Brown ◽  
Dominique H. Limoli ◽  
Vanessa V. Phelan ◽  
George A. O’Toole
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Physical Space ◽  
Late Time ◽  
Protective Effects ◽  
Content Type ◽  
Alginate Production ◽  
The Impact

ABSTRACT Cystic fibrosis (CF) patients chronically infected with both Pseudomonas aeruginosa and Staphylococcus aureus have worse health outcomes than patients who are monoinfected with either P. aeruginosa or S. aureus. We showed previously that mucoid strains of P. aeruginosa can coexist with S. aureus in vitro due to the transcriptional downregulation of several toxic exoproducts typically produced by P. aeruginosa, including siderophores, rhamnolipids, and HQNO (2-heptyl-4-hydroxyquinoline N-oxide). Here, we demonstrate that exogenous alginate protects S. aureus from P. aeruginosa in both planktonic and biofilm coculture models under a variety of nutritional conditions. S. aureus protection in the presence of exogenous alginate is due to the transcriptional downregulation of pvdA, a gene required for the production of the iron-scavenging siderophore pyoverdine as well as the downregulation of the PQS (Pseudomonas quinolone signal) (2-heptyl-3,4-dihydroxyquinoline) quorum sensing system. The impact of exogenous alginate is independent of endogenous alginate production. We further demonstrate that coculture of mucoid P. aeruginosa with nonmucoid P. aeruginosa strains can mitigate the killing of S. aureus by the nonmucoid strain of P. aeruginosa, indicating that the mechanism that we describe here may function in vivo in the context of mixed infections. Finally, we investigated a panel of mucoid clinical isolates that retain the ability to kill S. aureus at late time points and show that each strain has a unique expression profile, indicating that mucoid isolates can overcome the S. aureus-protective effects of mucoidy in a strain-specific manner. IMPORTANCE CF patients are chronically infected by polymicrobial communities. The two dominant bacterial pathogens that infect the lungs of CF patients are P. aeruginosa and S. aureus, with ∼30% of patients coinfected by both species. Such coinfected individuals have worse outcomes than monoinfected patients, and both species persist within the same physical space. A variety of host and environmental factors have been demonstrated to promote P. aeruginosa-S. aureus coexistence, despite evidence that P. aeruginosa kills S. aureus when these organisms are cocultured in vitro. Thus, a better understanding of P. aeruginosa-S. aureus interactions, particularly mechanisms by which these microorganisms are able to coexist in proximal physical space, will lead to better-informed treatments for chronic polymicrobial infections.

scholarly journals In Vitro Synergy and In Vivo Activity of Tigecycline-Ciprofloxacin Combination Therapy against Vibrio vulnificus Sepsis

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Seong Eun Kim ◽  
Hee Kyung Kim ◽  
Su-Mi Choi ◽  
Yohan Yu ◽  
Uh Jin Kim ◽  
...  
Keyword(s):  
Survival Rate ◽  
Mortality Rate ◽  
Combination Therapy ◽  
Combination Treatment ◽  
Vibrio Vulnificus ◽  
Antibiotic Regimen ◽  
Content Type ◽  
Time Kill

ABSTRACT The mortality rate associated with Vibrio vulnificus sepsis remains high. An in vitro time-kill assay revealed synergism between tigecycline and ciprofloxacin. The survival rate was significantly higher in mice treated with tigecycline plus ciprofloxacin than in mice treated with cefotaxime plus minocycline. Thus, combination treatment with tigecycline-ciprofloxacin may be an effective novel antibiotic regimen for V. vulnificus sepsis.

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