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Sample records for bioadhesive controlled metronidazole

  1. Development and Characterization of Bioadhesive Gel of Microencapsulated Metronidazole for Vaginal Use

    PubMed Central

    Bhabani Shankar, Nayak; Prasant Kumar, Rout; Udaya Kumar, Nayak; Benoy Brata, Bhowmik

    2010-01-01

    The present study concerned with the development and characterization of metronidazole microcapsules prepared by thermal change method using different ratios (1:1, 1:2 and 1:4) of ethyl cellulose in order to select the best microcapsule formulation with a good encapsulation efficiency and drug release profile. The obtained microcapsules were discrete, spherical with free flowing properties and evaluated for particle size, shape, flow properties, wall thickness, drug encapsulation efficiency and in vitro release performance. The drug carrier interactions were investigated in solid state by FT-IR spectroscopy and scanning electron microscopy. The microcapsules with a narrow size range of 23-68 μm showed higher encapsulation efficiency. The selected microcapsule formulation, MC3 (Drug polymer ratio 1:4) was employed for gel formulation with a variety of carbopol polymers (carbopol-934, 940, 974 and 980) by mechanical stirring method in order to develop a sustained release microencapsulated metronidazole microcapsules-containing bioadhesive gel. The prepared bioadhesive gels were evaluated for pH, spreadability, extrudability, viscosity, vaginal irritation, in vitro drug release, bioadhesion, accelerated stability and in vitro drug release kinetic. In vitro experiments indicated a sustained release over 24 h and an acceptable bioadhesion quality for formulation F3. Hence, it can be concluded that the formulation F3 has potential to deliver metronidazole in a controlled and constant manner for prolong period over other formulations and can be adopted for a successful delivery of metronidazole for vaginal use. PMID:24363730

  2. Formulation Optimization of Hydrodynamically Balanced Oral Controlled Release Bioadhesive Tablets of Tramadol Hydrochloride

    PubMed Central

    Singh, Bhupinder; Rani, Ashu; Babita; Ahuja, Naveen; Kapil, Rishi

    2010-01-01

    The directly compressible floating-bioadhesive tablets of tramadol were formulated using varying amounts Carbopol 971P (CP) and hydroxy-propylmethyl cellulose (HPMC), along with other requisite excipients. In vitro drug release profile, floatational characteristics and ex vivo bioadhesive strength using texture analyzer were determined, and systematically optimized using a 32 central composite design (CCD). The studies indicated successful formulation of gastroretentive compressed matrices with excellent controlled release, mucoadhesion and hydrodynamic balance. Comparison of the dissolution profiles of the optimized formulation, with optimal composition of CP:HPMC :: 80.0:125.0, with that of the marketed controlled release formulation other indicated analogy of drug release performance with each other. Validation of optimization study using eight confirmatory experimental runs indicated very high degree of prognostic ability of CCD with mean ± SEM of −0.06% ± 0.37. Further, the study successfully unravels the effect of the polymers on the selected response variables. PMID:21179349

  3. Formulation development and evaluation of metronidazole magnetic nanosuspension as a magnetic-targeted and polymeric-controlled drug delivery system

    NASA Astrophysics Data System (ADS)

    Latha, Subbiah; Selvamani, Palanisamy; Kumar, Chelladurai Senthil; Sharavanan, Palaniappan; Suganya, Govindan; Beniwal, Vijender Singh; Rao, Poduri Rama

    2009-05-01

    A nanosuspension of magnetically tagged metronidazole was developed by the solvent displacement method coupled with ultrasonication and was evaluated for its physicochemical properties. The drug release from metronidazole magnetic nanosuspension at pH 1.2 and 7.0 shows maximum correlation coefficient for zero order and Higuchi model, respectively. The anthelmintic activity of the formulated metronidazole magnetic nanosuspension was evaluated on Indian earthworms (Pheretima poi). Metronidazole magnetic nanosuspension at a dose of 10 and 50 mg/ml shortened by 31% and 34%, respectively, the mean time to death of the earthworms when compared against a non-magnetic metronidazole suspension. Thus, the developed metronidazole magnetic nanosuspension showed potent, controlled and targeted drug action and might be a good therapeutic avenue in combating infectious GI disorders.

  4. MULTI-RESERVOIR BIOADHESIVE MICRODEVICES FOR INDEPENDENT RATE-CONTROLLED DELIVERY OF MULTIPLE DRUGS

    PubMed Central

    Chirra, Hariharasudhan D.; Desai, Tejal A.

    2012-01-01

    A variety of oral administrative systems such as enterically coated tablets, capsules, particles, and liposomes have been developed to improve oral bioavailability of drugs. However, they suffer from poor intestinal localization and therapeutic efficacy due to the various physiological conditions and high shear fluid flow. Fabrication of novel microdevices combined with the introduction of controlled release, improved adhesion, selective targeting, and tissue permeation may overcome these issues and potentially diminish the toxicity and high frequency of conventional oral administration. Herein, thin, asymmetric, poly(methyl methacrylate); PMMA microdevices were fabricated with multiple reservoirs using photolithography and reactive ion etching. They were loaded with different individual model drug in each reservoir. Enhanced bioadhesion of the microdevices was observed in the presence of a conjugated of targeting protein; tomato lectin to the PMMA surface. As compared to drug encompassing hydrogels, an increase in drug permeation across the caco-2 monolayer was noticed in the presence of a microdevice loaded with the same drug-hydrogel system. Also, the release of multiple drugs from their respective reservoirs was found to be independent from each other. The use of different hydrogel systems in each reservoir showed differences in the controlled release of the respective drugs over the same period of release. These results suggest that in the future, the microfabricated unidirectional multi-drug releasing devices will have an impact over the oral administration of a broad range of therapeutics. PMID:22962019

  5. Evaluation of buccoadhesive metronidazole tablets: microbiological response.

    PubMed

    Ahuja, A; Khar, R K; Chaudhry, R

    1998-04-01

    Metronidazole has been found beneficial in a number of oro-dental infections namely dry socket, gingivitis, smelling tumours and periodontal diseases where anaerobes are implicated as pathogens. Buccoadhesive tablets of metronidazole were prepared by compressing the drug, bioadhesive polymers namely Carbopol-934P, a cellulose ether derivative, mannitol and suitable flavouring and sweetening agents. The tablet showed good release in vitro. It was subjected to in-situ release studies using bovine cheek pouch membrane in a flow through cell. The concentration was found to be above the MIC of the drug over the entire period of the release studies. The samples were tested against anaerobic strains commonly found in oro-dental infections. Since anaerobes are very slow growing microorganisms, a method for testing their susceptibility to metronidazole solutions was developed which can be used for other bioadhesive formulations which are active against anaerobes. PMID:9583086

  6. Metronidazole Oral

    MedlinePlus

    Metronidazole eliminates bacteria and other microorganisms that cause infections of the reproductive system, gastrointestinal tract, skin, vagina, and other areas of the body. Antibiotics will not work ...

  7. Metronidazole Topical

    MedlinePlus

    Metronidazole comes as a cream, lotion, or gel to be applied to your skin and as a gel to be used in the vagina. Metronidazole usually is ... the medication. Apply a thin layer of cream, lotion, or gel and rub it gently into the ...

  8. Adjustable bioadhesive control of PEGylated hyperbranch brushes on polystyrene microplate interface for the improved sensitivity of human blood typing.

    PubMed

    Chen, Yan-Wen; Chang, Yung; Lee, Rong-Ho; Li, Wen-Tyng; Chinnathambi, Arunachalam; Alharbi, Sulaiman Ali; Hsiue, Ging-Ho

    2014-08-01

    A PEGylated 96-well polystyrene (PS) microplate was first introduced for applications in high-throughput screening for selective blood typing to minimize the risks in blood transfusions. Herein, we present a hemocompatible PS 96-well microplate with adjustable PEGylated hyperbranch brush coverage prepared by ozone pretreated activation and thermally induced surface PEGylation. The grafting properties, hydration capacity, and blood compatibility of the PEGylated hyperbrush immobilized PS surfaces in human blood were illustrated by the combined chemical and physical properties of the surface, and the dependence of the specific absorption of human plasma fibrinogen onto the PEGylated surfaces on the grafting density was analyzed by monoclonal antibodies. The surface coverage of PEGylated brushes plays a major role in the bioadhesive properties of modified PS microplates, which in turn control the level of agglutination sensitivity in blood typing. The bioadhesive resistance toward proteins, platelets, and erythrocytes in human whole blood showed a correlation to the controlled hydration properties of the PEGylated hyperbrush-modified surfaces. Therefore, we suggested that the surface coverage of PEGylated hyperbrushes on PS surfaces can increase the sensitivity of cross-matching blood agglutination by up to 16-fold compared to that of the conventional 96-well virgin PS due to the regulated biorecognition of hematocrit and antibodies of the PEGylated hyperbrush-modified surfaces. PMID:25022949

  9. Metronidazole Oral

    MedlinePlus

    ... microorganisms that cause infections of the reproductive system, gastrointestinal tract, skin, vagina, and other areas of the ... are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking metronidazole, call ...

  10. Development and evaluation of acid-buffering bioadhesive vaginal tablet for mixed vaginal infections.

    PubMed

    Alam, Mohd Aftab; Ahmad, Farhan Jalees; Khan, Zeenat Iqbal; Khar, Roop Krishen; Ali, Mushir

    2007-01-01

    An acid-buffering bioadhesive vaginal tablet was developed for the treatment of genitourinary tract infections. From the bioadhesion experiment and release studies it was found that polycarbophil and sodium carboxymethylcellulose is a good combination for an acid-buffering bioadhesive vaginal tablet. Sodium monocitrate was used as a buffering agent to provide acidic pH (4.4), which is an attribute of a healthy vagina. The effervescent mixture (citric acid and sodium bicarbonate) along with a superdisintegrant (Ac-Di-sol) was used to enhance the swellability of the bioadhesive tablet. The drugs clotrimazole (antifungal) and metronidazole (antiprotozoal as well as an antibacterial) were used in the formulation along with Lactobacillus acidophilus spores to treat mixed vaginal infections. From the ex vivo retention study it was found that the bioadhesive polymers hold the tablet for more than 24 hours inside the vaginal tube. The hardness of the acid-buffering bioadhesive vaginal tablet was optimized, at 4 to 5 kg hardness the swelling was found to be good and the cumulative release profile of the developed tablet was matched with a marketed conventional tablet (Infa-V). The in vitro spreadability of the swelled tablet was comparable to the marketed gel. In the in vitro antimicrobial study it was found that the acid-buffering bioadhesive tablet produces better antimicrobial action than marketed intravaginal drug delivery systems (Infa-V, Candid-V and Canesten 1). PMID:18181530

  11. Bioadhesive okra polymer based buccal patches as platform for controlled drug delivery.

    PubMed

    Kaur, Gurpreet; Singh, Deepinder; Brar, Vivekjot

    2014-09-01

    In the present investigation, polysaccharide from the Okra fruits (Hibiscus esculentus) was extracted, characterized and explored for its mucoadhesive potential. Mucoadhesive films of okra polymer (OP) were prepared by solvent casting method based on 3(2) factorial design. For these studies, OP (2.0%, 2.5%, 3.0%, w/v) and glycerol (plasticizer) (0.25%, 0.50%, 0.75%, v/v) were taken as independent variables while tensile strength, mucoadhesive strength, contact angle, swelling index and residence time as dependent variables. The developed films were evaluated for their physicochemical, mechanical and electrical properties. The formulated films were found to be smooth, flexible, and displayed adequate mucoadhesive and tensile strength. Their near neutral pH and negative hemolytic studies indicated their non-irritability and biocompatible nature with biological tissues. The formulation comprising of 3% OP and 0.5% glycerol (F8) was found to exhibit optimum mechanical properties. Further, optimized film was loaded with zolmitriptan (model drug) to determine its drug release profiles. In vitro and ex vivo drug release studies demonstrated a controlled release of zolmitriptan over a period of 8h in simulated salivary fluid (SSF) pH 6.8, with the correlation coefficient values indicating its non-Fickian kinetics. Thus, OP can be used as a promising biomaterial for controlled drug delivery. PMID:25036601

  12. Preparation and characterization of bioadhesive controlled-release gels of cidofovir for vaginal delivery.

    PubMed

    Tuğcu-Demiröz, Fatmanur; Acartürk, Füsun; Özkul, Aykut

    2015-01-01

    The aim of this study was to develop mucoadhesive and thermosensitive gels for vaginal delivery that would be able to provide a controlled release of the model drug, cidofovir. The study also monitored the drug's potential antiviral properties. Cidofovir was put into the form of a vaginal gel, using mucoadhesive and thermosensitive polymers such as chitosan, Carbopol 974P, HPMC, and poloxamer 407. The physicopharmaceutical properties and stability of the vaginal gel formulations were evaluated. The gel formulation which was prepared with HPMC K100M exhibited the highest viscosity, as well as maximum adhesiveness, cohesiveness, and mucoadhesion values. The results of antiviral activity studies, which used the bovine herpes virus type 1 virus infection in vitro model using Vero cells, demonstrated the antiherpetic effect of the cidofovir gel containing HPMC K100M, at least under in vitro conditions. The study found that a mucoadhesive vaginal gel containing cidofovir can be a promising and innovative alternative therapeutic system for the treatment of genital herpes simplex virus and human papilloma virus induced infections in women. PMID:26300445

  13. Metronidazole induced cerebellar ataxia

    PubMed Central

    Hari, Aditya; Srikanth, B. Akshaya; Lakshmi, G. Sriranga

    2013-01-01

    Metronidazole is a widely used antimicrobial usually prescribed by many specialist doctors for a short duration of 10-15 days. Prolonged use of metronidazole is rare. The present case is of a patient who used the drug for 4 months and developed peripheral neuropathy, convulsions, and cerebellar ataxia. He was treated with diazepam and levetiracetam. The patient recovered completely following discontinuation of metronidazole. PMID:23833378

  14. Design Strategies and Applications of Tissue Bioadhesives

    PubMed Central

    Mehdizadeh, Mohammadreza; Yang, Jian

    2013-01-01

    In the past two decades tissue adhesives and sealants have revolutionized hemostasis and wound management in traumatic and surgical injuries. Various biological-driven glues and synthetic adhesives are clinically utilized either as an adjunct to conventional hemostats and wound closure techniques, such as suturing, or as a replacement to them. The ability to effectively and promptly control bleeding, thus, reducing the risk of complications due to severe blood loss, in addition to convenience of use render medical adhesive a highly suitable tool for wound management. This review focuses on existing tissue adhesive systems, their structure, functioning mechanism, indicated and off-label applications, and limitations. It also includes the latest advances in the development of new tissue adhesives as well as the emerging applications in regenerative medicine. We expect that this review will provide insightful discussion on tissue bioadhesive design and lead to innovations for the development of the next generation of tissue bioadhesives and their related biomedical applications. PMID:23225776

  15. Bioadhesive Films Containing Fluconazole for Mucocutaneous Candidiasis

    PubMed Central

    Patel, S. K.; Shah, D. R.; Tiwari, S.

    2015-01-01

    Fluconazole is a broad spectrum antifungal agent that has been extensively applied for the management of oral, pharyngeal and cutaneous candidiasis. Fluconazole has a high volume of distribution (0.55–0.65 l/kg) and has systemic toxicity due to high drug-drug interaction. The present study focuses on the formulation of bioadhesive film as a controlled release carrier for fluconazole. The formulation was intended to provide localized delivery of fluconazole exclusively at the site of infection, thereby reducing its total dose and hence, dose-related toxicities. Bioadhesive films were prepared by solvent casting method using sodium alginate and polyvinyl alcohol alone as well as in various combinations. Prepared films were evaluated for physical characteristics like, weight and content uniformity, film thickness, swelling index, microenvironment pH and folding endurance. In vitro drug release, in vitro and ex vivo residence time, bioadhesive strength and skin irritation were also studied. Accelerated stability study was conducted on the optimized formulation as per ICH guidelines. Weight of all the films were not more than 20 mg. Thickness of the films ranged between 0.09 to 0.15 mm whereas swelling indices showed a high extent of variation. Films composed of polyvinyl alcohol alone provided a swelling index of 6%. Bioadhesive strength was found to be more than 18 g. Microenvironment pH was near to 7.0 for most of the formulations. Ex vivo residence time of optimized batch was more than 5 h and it provided controlled drug release up to 8 h. As revealed in FT-IR and DSC studies, drug was found to be compatible with the excipients used in this study. PMID:25767319

  16. Metronidazole (Flagyl) and Pregnancy

    MedlinePlus

    ... shown to cause changes in genetic material and cancer in animals. At this time, it has not been found to have these effects in humans. One study that followed several hundred women for 20 years did not find an increase in cancer. Can I take metronidazole while breastfeeding? Metronidazole gets ...

  17. Amoxicillin Plus Metronidazole Therapy for Patients with Periodontitis and Type 2 Diabetes: A 2-year Randomized Controlled Trial.

    PubMed

    Tamashiro, N S; Duarte, P M; Miranda, T S; Maciel, S S; Figueiredo, L C; Faveri, M; Feres, M

    2016-07-01

    The aim of this study was to assess the changes occurring in subgingival biofilm composition and in the periodontal clinical parameters of subjects with periodontitis and type 2 diabetes mellitus (DM) treated by means of scaling and root planing (SRP) only or combined with systemic metronidazole (MTZ) and amoxicillin (AMX). Fifty-eight subjects were randomly assigned to receive SRP only (n = 29) or with MTZ (400 mg/thrice a day [TID]) and AMX (500 mg/TID) (n = 29) for 14 d. Six subgingival plaque samples/subject were analyzed by checkerboard DNA-DNA hybridization for 40 bacterial species at baseline and 3 mo, 1 y, and 2 y posttherapy. At 2 y posttherapy, the antibiotic-treated group harbored lower mean proportions (5.5%) of red complex pathogens than the control group (12.1%) (P < 0.05). The proportions of the Actinomyces species remained stable in the antibiotic group but showed a statistically significant reduction in the control group from 1 to 2 y in subjects achieving a low risk clinical profile for future disease progression (i.e., ≤4 sites with probing depth [PD] ≥5 mm). The test group also had a lower mean number of sites with PD ≥5 mm (3.5 ± 3.4) and a higher percentage of subjects reaching the low risk clinical profile (76%) than the control group (14.7 ± 13.1 and 22%, respectively) (P < 0.05) at 2 y posttreatment. MTZ + AMX intake was the only significant predictor of subjects achieving the low risk at 2 y (odds ratio, 20.9; P = 0.0000). In conclusion, the results of this study showed that the adjunctive use of MTZ + AMX improves the microbiological and clinical outcomes of SRP in the treatment of subjects with generalized chronic periodontitis and type 2 DM up to 2 y (ClinicalTrials.gov NCT02135952). PMID:27013640

  18. Photocurable bioadhesive based on lactic acid.

    PubMed

    Marques, D S; Santos, J M C; Ferreira, P; Correia, T R; Correia, I J; Gil, M H; Baptista, C M S G

    2016-01-01

    Novel photocurable and low molecular weight oligomers based on l-lactic acid with proven interest to be used as bioadhesive were successfully manufactured. Preparation of lactic acid oligomers with methacrylic end functionalizations was carried out in the absence of catalyst or solvents by self-esterification in two reaction steps: telechelic lactic acid oligomerization with OH end groups and further functionalization with methacrylic anhydride. The final adhesive composition was achieved by the addition of a reported biocompatible photoinitiator (Irgacure® 2959). Preliminary in vitro biodegradability was investigated by hydrolytic degradation in PBS (pH=7.4) at 37 °C. The adhesion performance was evaluated using glued aminated substrates (gelatine pieces) subjected to pull-to-break test. Surface energy measured by contact angles is lower than the reported values of the skin and blood. The absence of cytoxicity was evaluated using human fibroblasts. A notable antimicrobial behaviour was observed using two bacterial models (Staphylococcus aureus and Escherichia coli). The cured material exhibited a strong thrombogenic character when placed in contact with blood, which can be predicted as a haemostatic effect for bleeding control. This novel material was subjected to an extensive characterization showing great potential for bioadhesive or other biomedical applications where biodegradable and biocompatible photocurable materials are required. PMID:26478350

  19. Stability of Metronidazole Suspensions.

    PubMed

    Donnelly, Ronald F; Ying, James

    2015-01-01

    Metronidazole is an antiprotozoal agent used in the treatment of bacterial and protozoal anaerobic infections. The objectives of this study were to develop concentrated metronidazole suspensions that are inexpensive and easy to prepare and determine the stability of these suspensions after storage in amber polyvinyl chloride bottles at room temperature (23°C) and under refrigeration (5°C). Metronidazole suspensions (50 mg/mL) were prepared from powder using Ora-Blend or simple syrup as the vehicles. Samples were collected in triplicate from each container on days 0, 7, 14, 28, 56, and 93. Samples were assayed using a high-performance liquid chromatography method that had been validated as stability indicating. Color, change in physical appearance, and pH were also monitored at each time interval. There was no apparent change in color or physical appearance. The pH values changed by less than 0.20 units over the 93 days. The stability of metronidazole suspensions compounded from United States Pharmacopeia powder using Ora-Blend or simple syrup and packaged in amber polyvinyl chloride bottles was determined to be 93 days when stored at either room temperature or under refrigeration. PMID:26714365

  20. The use of metronidazole and amoxicillin in the treatment of advanced periodontal disease. A prospective, controlled clinical trial.

    PubMed

    Berglundh, T; Krok, L; Liljenberg, B; Westfelt, E; Serino, G; Lindhe, J

    1998-05-01

    The present clinical trial was performed to study the effect of systemic administration of metronidazole and amoxicillin as an adjunct to mechanical therapy in patients with advanced periodontal disease. 16 individuals, 10 female and 6 male, aged 35-58 years, with advanced periodontal disease were recruited. A baseline examination included assessment of clinical, radiographical, microbiological and histopathological characteristics of periodontal disease. The 16 patients were randomly distributed into 2 different samples of 8 subjects each. One sample of subjects received during the first 2 weeks of active periodontal therapy, antibiotics administered via the systemic route (metronidazole and amoxicillin). During the corresponding period, the 2nd sample of subjects received a placebo drug (placebo sample). In each of the 16 patients, 2 quadrants (1 in the maxilla and 1 in the mandible) were exposed to non-surgical subgingival scaling and root planing. The contralateral quadrants were left without subgingival instrumentation. Thus, 4 different treatment groups were formed; group 1: antibiotic therapy but no scaling, group 2: antibiotic therapy plus scaling, group 3: placebo therapy but no scaling, group 4: placebo therapy plus scaling. Re-examinations regarding the clinical parameters were performed, samples of the subgingival microbiota harvested and 1 soft tissue biopsy from 1 scaled and 1 non-scaled quadrant obtained 2 months and 12 months after the completion of active therapy. The teeth included in groups 1 and 3 were following the 12-month examination exposed to non-surgical periodontal therapy, and subsequently exited from the study. Groups 2 and 4 were also re-examined 24 months after baseline. The findings demonstrated that in patients with advanced periodontal disease, systemic administration of metronidazole plus amoxicillin resulted in (i) an improvement of the periodontal conditions, (ii) elimination/suppression of putative periodontal pathogens such as

  1. Fabrication of a bioadhesive transdermal device from chitosan and hyaluronic acid for the controlled release of lidocaine.

    PubMed

    Anirudhan, T S; Nair, Syam S; Nair, Anoop S

    2016-11-01

    A novel efficient transdermal (TD) lidocaine (LD) delivery device based on chitosan (CS) and hyaluronic acid (HA) was successfully developed in the present investigation. CS was grafted with glycidyl methacrylate (GMA) and butyl methacrylate (BMA) to fabricate a versatile material with improved adhesion and mechanical properties. HA was hydrophobically modified by covalently conjugating 3-(dimethylamino)-1-propylamine (DMPA) to encapsulate poorly water soluble LD and was uniformly dispersed in modified CS matrix. The prepared materials were characterized through FTIR, NMR, XRD, SEM, TEM and tensile assay. The dispersion of amine functionalized HA (AHA) on modified CS matrix offered strong matrix - filler interaction, which improved the mechanical properties and drug retention behavior of the device. In vitro skin permeation study of LD was performed with modified Franz diffusion cell using rat skin and exhibited controlled release. The influence of storage time on release profile was investigated and demonstrated that after the initial burst, LD release profile of the device after 30 and 60days storage was identical to that of a device which was not stored. In vivo skin adhesion test and skin irritation assay in human subjects, water vapor permeability and environmental fitness test was performed to judge its application in biomedical field. All results displayed that the fabricated device is a potential candidate for TD LD administration to the systemic circulation. PMID:27516320

  2. Bioadhesion: new possibilities for drug administration?

    PubMed

    Woodley, J

    2001-01-01

    Bioadhesion (and mucoadhesion) is the process whereby synthetic and natural macromolecules adhere to mucosal surfaces in the body. If these materials are then incorporated into pharmaceutical formulations, drug absorption by mucosal cells may be enhanced or the drug released at the site for an extended period of time. For synthetic polymers, such as the chitosans, carbopols and carbomers, the mechanism of bio/mucoadhesion is the result of a number of different physicochemical interactions. Biological bio/mucoadhesives, such as plant lectins, show specific interactions with cell surfaces and mucin and are seen as the 'second generation' bioadhesives. Bioadhesive systems for drug administration via the buccal and nasal cavities are nearing the market; in the case of nasal bioadhesion, bioadhesive microparticles are used. A bioadhesive formulation for drug administration to the vagina is in use. The gastrointestinal tract is proving a more difficult site because of the rapid turnover of mucus, and relatively constant transit time, but intensive research is in progress. Micro- and nano-particles, coated with either bio/mucoadhesive polymers or specific biological bioadhesives, are showing some promise, but will require considerable research and development before reaching the market. PMID:11286325

  3. Comparative Evaluation of Sustained Release Collagen Device Containing 5% Metronidazole (Metrogene) along With and Without Scaling and Root Planing at Regular Intervals with Treatment of Chronic Periodontitis: A Case Control Study

    PubMed Central

    Paul, Tony P; Emmatty, Rishi; Pulikkottil, Joseph J; Rahman, Aslam Abdul; Kumar, S Arun; George, Neethu

    2015-01-01

    Background: A short-term study was undertaken with an objective to demonstrate the therapeutic benefit resulting from the use of Metronidazole sponges combined with and without mechanical debridement to mechanical treatment alone in the treatment of periodontal pockets in chronic periodontitis. Materials and Methods: The study compared the plaque index, gingival index, sulcus bleeding index and probing pocket depth in twenty control sites that received superficial scaling and root planing without the local drug delivery with experimental site A (20 sites that received local drug delivery (5% metronidazole) without superficial scaling and root planing) and experimental site B (20 sites received superficial scaling, root planing and local drug delivery (5% metronidazole) at “0” day, 15th day and 30th day. Results: There was a significant reduction in plaque index, gingival index, sulcus bleeding index and probing pocket depth in both experimental sites A and B at different intervals from the baseline. Conclusion: From the above conclusions, it can be suggested that a single subgingival application of 5% metronidazole in a collagen carrier can be effective, when associated with debridement in the treatment of adult periodontitis. PMID:26124594

  4. Evaluation of mechanical and rheological properties of metronidazole gel as local delivery system.

    PubMed

    Jelvehgari, Mitra; Montazam, Hassan

    2011-06-01

    Rosacea is a chronic multifactorial vascular skin disorder that affects about 10 percent of the general population. Metronidazole is an effective antibiotic in the treatment of moderate-to severe rosacea. Metronidazole is a suitable drug in cases of resistance to tetracycline or erythromycin, but it has also been shown that oral metronidazole may increase the side effects (e.g., peripheral neuropathy). Oral metronidazole should not be used for more than three months, and hence topical metronidazole gel is the best therapeutic choice in rosacea (especially during pregnancy). This study examined the mechanical (adhesiveness, cohesiveness, extrudability, spreadability, homogeneity) and rheological (viscosity), skin irritant and drug release properties of different metronidazole gel formulations that contain anionic emulsifying wax, glycerin and lactic acid in different proportions. The release studies were conducted using Franz diffusion cells and Silastic membrane as a barrier. The results indicated that gel compressibility, hardness, and adhesiveness, are the factors that influence the ease of gel removal from the container, ease of gel application onto the mucosal membrane, and gel bioadhesion. The findings showed that there exists a strong negative correlation between the spreadability of a formulation and its cohesiveness, the spreadability of a formulation is inversely proportional to its cohesiveness. However, sorbitol solution (70%) concentration was not significantly correlated with drug release. In addition, drug release was significantly reduced as the concentration of anionic emulsifying wax increased and the concentration of lactic acid decreased. The maximum metronidazole release was achieved at a pH of 4-6. Data obtained from in vitro release studies were fitted to various kinetic models and high correlation was obtained in the Higuchi and first order models. The results showed that all the gel formulations showed good extrudability, viscosity

  5. Microscale Bioadhesive Hydrogel Arrays for Cell Engineering Applications.

    PubMed

    Patel, Ravi Ghanshyam; Purwada, Alberto; Cerchietti, Leandro; Inghirami, Giorgio; Melnick, Ari; Gaharwar, Akhilesh K; Singh, Ankur

    2014-09-01

    Bioengineered hydrogels have been explored in cell and tissue engineering applications to support cell growth and modulate its behavior. A rationally designed scaffold should allow for encapsulated cells to survive, adhere, proliferate, remodel the niche, and can be used for controlled delivery of biomolecules. Here we report a microarray of composite bioadhesive microgels with modular dimensions, tunable mechanical properties and bulk modified adhesive biomolecule composition. Composite bioadhesive microgels of maleimide functionalized polyethylene glycol (PEG-MAL) with interpenetrating network (IPN) of gelatin ionically cross-linked with silicate nanoparticles were engineered by integrating microfabrication with Michael-type addition chemistry and ionic gelation. By encapsulating clinically relevant anchorage-dependent cervical cancer cells and suspension leukemia cells as cell culture models in these composite microgels, we demonstrate enhanced cell spreading, survival, and metabolic activity compared to control gels. The composite bioadhesive hydrogels represent a platform that could be used to study independent effect of stiffness and adhesive ligand density on cell survival and function. We envision that such microarrays of cell adhesive microenvironments, which do not require harsh chemical and UV crosslinking conditions, will provide a more efficacious cell culture platform that can be used to study cell behavior and survival, function as building blocks to fabricate 3D tissue structures, cell delivery systems, and high throughput drug screening devices. PMID:25328548

  6. Bioadhesive properties and biodistribution of cyclodextrin-poly(anhydride) nanoparticles.

    PubMed

    Agüeros, Maite; Areses, Paloma; Campanero, Miguel Angel; Salman, Hesham; Quincoces, Gemma; Peñuelas, Ivan; Irache, Juan Manuel

    2009-06-28

    This work describes the preparation, characterization and evaluation of the nanoparticles formed by the copolymer of methyl vinyl ether and maleic anhydride (Gantrez) AN) and cyclodextrins, including beta-cyclodextrin (CD) hydroxypropyl-beta-cyclodextrin (HPCD) and 6-monodeoxy-6-monoamino-beta-cyclodextrin (NHCD). The cyclodextrin-poly(anhydride) nanoparticles were prepared by a solvent displacement method and characterized by measuring the size, zeta potential, morphology and composition. For bioadhesion studies, nanoparticles were fluorescently labelled with rhodamine B isothiocianate (RBITC). For in vivo imaging biodistribution studies, (99m)Tc-labelled nanoparticles were used. Nanoparticles displayed a size of about 150nm and a cyclodextrin content which was found optimal under the following experimental conditions: cyclodextrin/poly(anhydride) ratio of 0.25 by weight, 30min of incubation time between the cyclodextrin and the polymer. Moreover, the oligosaccharide content was higher with CD than with NHCD and HPCD. Overall, cyclodextrin-poly(anhydride) nanoparticles displayed homogeneous bioadhesive interactions within the gut. The intensity of these interactions was higher than for control nanoparticles. The high bioadhesive capacity was observed for HPCD-NP and NHCD-NP which can be related with their rough morphology and, thus, a higher specific surface than for smooth nanoparticles (CD-NP). Finally, from in vivo studies, no evidence of translocation of distribution to other organs was observed when these nanoparticles were orally administered. PMID:19491010

  7. Bioadhesive Mini-Tablets for Vaginal Drug Delivery

    PubMed Central

    Hiorth, Marianne; Nilsen, Susanne; Tho, Ingunn

    2014-01-01

    Different non-ionic cellulose ethers (methyl cellulose, MC; hydroxyethyl cellulose, HEC; hydroxypropyl cellulose, HPC; hydroxypropylmethyl cellulose, HPMC) and microcrystalline cellulose (MCC) were investigated as matrix formers for preparation of mini-tablets targeting vaginal drug delivery. Hexyl aminolevulinat hydrochloridum (HAL) was used as a model drug. The mini-tablets were characterized with respect to their mechanical strength, bioadhesion towards cow vaginal tissue in two independent tests (rotating cylinder test, detachment test using texture analyzer), and dissolution rate in two media mimicking the pH levels of fertile, healthy and post-menopausal women (vaginal fluid simulant pH 4.5, phosphate buffer pH 6.8). Mini-tablets with a matrix of either HPMC or HPC were found to possess adequate mechanical strength, superior bioadhesive behavior towards vaginal tissue, and pH independent controlled release of the model drug, suggesting that both systems would be suited for the treatment of women regardless of age, i.e., respective of their vaginal pH levels. Bioadhesive mini-tablets offer a potential for improved residence time in the vaginal cavity targeting contact with mucosal tissue and prolonged release of the drug. PMID:25166286

  8. Metronidazole-Induced Cerebellar Toxicity

    PubMed Central

    Agarwal, Amit; Kanekar, Sangam; Sabat, Shyam; Thamburaj, Krishnamurthy

    2016-01-01

    Metronidazole is a very common antibacterial and antiprotozoal with wide usage across the globe, including the least developed countries. It is generally well-tolerated with a low incidence of serious side-effects. Neurological toxicity is fairly common with this drug, however majority of these are peripheral neuropathy with very few cases of central nervous toxicity reported. We report the imaging findings in two patients with cerebellar dysfunction after Metronidazole usage. Signal changes in the dentate and red nucleus were seen on magnetic resonance imaging in these patients. Most of the cases reported in literature reported similar findings, suggesting high predilection for the dentate nucleus in metronidazole induced encephalopathy. PMID:27127600

  9. Injectable Bioadhesive Hydrogels with Innate Antibacterial Properties

    PubMed Central

    Giano, Michael C.; Ibrahim, Zuhaib; Medina, Scott H.; Sarhane, Karim A.; Christensen, Joani M.; Yamada, Yuji; Brandacher, Gerald; Schneider, Joel P.

    2014-01-01

    Surgical site infections cause significant postoperative morbidity and increased healthcare costs. Bioadhesives used to fill surgical voids and support wound healing are typically devoid of antibacterial activity. Here, we report novel syringe-injectable bioadhesive hydrogels with inherent antibacterial properties prepared from mixing polydextran aldehyde (PDA) and branched polyethylenimine (PEI). These adhesives kill both Gram-negative and Gram–positive bacteria, while sparing human erythrocytes. An optimal composition of 2.5 wt % oxidized dextran and 6.9 wt % PEI sets within seconds forming a mechanically rigid (~1700 Pa) gel offering a maximum adhesive stress of ~ 2.8 kPa. A murine infection model showed that the adhesive is capable of killing S. pyogenes introduced subcutaneously at the bioadhesive’s surface, with minimal inflammatory response. The adhesive was also effective in a cecal ligation and puncture model, preventing sepsis and significantly improving survival. These bioadhesives represent novel, inherently antibacterial materials for wound filling applications. PMID:24958189

  10. [Perioperative metronidazole-prophylaxis for cesarian section (author's transl].

    PubMed

    Gerstner, G; Kofler, E; Huber, J

    1980-12-01

    A prospective, randomized clinical trial was conducted in 103 patients undergoing cesarian section to assess the efficacy of prophylactic, intravenously administered Metronidazole on the infectious morbidity. A group of 53 patients with perioperative Metronidazol-prophylaxis was compared to a similar controll-group without prophylaxis. Bacteriologic swabs were taken from the cervix pre- and postoperatively, using anaerobic transport media. Prophylactic Metronidazole reduced postoperative fever of more than 38 degrees C on two subsequent days from 60% in the controll-group to 30,2% in the Metronidazole-group (p less than 0,01) wound infections were reduced from 18% without to 5,7% with prophylaxis (p less than 0,05) and Endometritis from 30% without to 13,2% with prophylaxis (p less than 0,05). An additional antibiotic therapy was necessary in 44% of the cases in the controllgroup, compared to 24,5% of the cases in the Metronidazolegroup (p less than 0,05). The mean duration of hospitalisation was reduced from 12,1 +/- 3,2 days in the controll-group to 11,2 +/- 2,1 in the Metronidazole-group (p less than 0,01). Anaerobic bacteria were isolated from the servical swabs in 60% preoperatively, with a still increasing incidence to 72% postoperatively, compared to 7% in the Metronidazole-group. Our results suggest, that prophylactic, intravenously administered Metronidazol reduces the infectious morbidity following cesarian section due to the reduction of the anaerobic flora at the female genital-tract. PMID:7222872

  11. Optical Spectroscopy of Marine Bioadhesive Interfaces

    NASA Astrophysics Data System (ADS)

    Barlow, Daniel E.; Wahl, Kathryn J.

    2012-07-01

    Marine organisms have evolved extraordinarily effective adhesives that cure underwater and resist degradation. These underwater adhesives differ dramatically in structure and function and are composed of multiple proteins assembled into functional composites. The processes by which these bioadhesives cure—conformational changes, dehydration, polymerization, and cross-linking—are challenging to quantify because they occur not only underwater but also in a buried interface between the substrate and the organism. In this review, we highlight interfacial optical spectroscopy approaches that can reveal the biochemical processes and structure of marine bioadhesives, with particular emphasis on macrofoulers such as barnacles and mussels.

  12. Injectable bioadhesive hydrogels with innate antibacterial properties

    NASA Astrophysics Data System (ADS)

    Giano, Michael C.; Ibrahim, Zuhaib; Medina, Scott H.; Sarhane, Karim A.; Christensen, Joani M.; Yamada, Yuji; Brandacher, Gerald; Schneider, Joel P.

    2014-06-01

    Surgical site infections cause significant postoperative morbidity and increased healthcare costs. Bioadhesives used to fill surgical voids and support wound healing are typically devoid of antibacterial activity. Here we report novel syringe-injectable bioadhesive hydrogels with inherent antibacterial properties prepared from mixing polydextran aldehyde and branched polyethylenimine. These adhesives kill both Gram-negative and Gram-positive bacteria, while sparing human erythrocytes. An optimal composition of 2.5 wt% oxidized dextran and 6.9 wt% polyethylenimine sets within seconds forming a mechanically rigid (~\

  13. Plasma hydroxy-metronidazole/metronidazole ratio in patients with liver disease and in healthy volunteers.

    PubMed

    Muscará, M N; Pedrazzoli, J; Miranda, E L; Ferraz, J G; Hofstätter, E; Leite, G; Magalhães, A F; Leonardi, S; De Nucci, G

    1995-11-01

    Metronidazole pharmacokinetics were studied in patients with different degrees of liver cirrhosis, classified according to the Child-Pugh algorithm (A, B or C, as liver disease severity increases) and in schistosomic patients. Metronidazole (500 mg) was administered i.v. as a slow infusion over 20 min, and blood samples were collected at set intervals after the end of the infusion. The plasma concentrations of metronidazole and its main metabolite hydroxy-metronidazole were quantified by reversed-phase h.p.l.c. with u.v. detection. The metronidazole and hydroxy-metronidazole areas under the curve from 0 to 24 h (AUC0,24h), the metronidazole terminal elimination half-life (t1/2), the total clearance (CL), the metronidazole volume of distribution (V) values and the hydroxy-metronidazole/metronidazole concentration ratios as a function of time were calculated for each group. Comparison of the metronidazole AUC0,24h, t1/2 and CL values revealed that metronidazole metabolism is progressively impaired as the severity of liver disease increases. There were no variations in these parameters between the schistosomic and Child-Pugh A groups. In addition, there were no differences in the V and hydroxy-metronidazole AUC0,24h among the various groups studied. However, metronidazole metabolism was delayed in patients with hepatic disease, as illustrated by the hydroxy-metronidazole/metronidazole ratio 10 min after the end of metronidazole infusion. These results indicate that the clinical assessment of liver disease is paralleled by an impairment of metronidazole metabolism. Of the studied variables, we propose the hydroxy-metronidazole/metronidazole ratio 10 min after metronidazole infusion as a suitable and practical index for liver function evaluation. PMID:8703652

  14. Plasma hydroxy-metronidazole/metronidazole ratio in patients with liver disease and in healthy volunteers.

    PubMed Central

    Muscará, M N; Pedrazzoli, J; Miranda, E L; Ferraz, J G; Hofstätter, E; Leite, G; Magalhães, A F; Leonardi, S; De Nucci, G

    1995-01-01

    Metronidazole pharmacokinetics were studied in patients with different degrees of liver cirrhosis, classified according to the Child-Pugh algorithm (A, B or C, as liver disease severity increases) and in schistosomic patients. Metronidazole (500 mg) was administered i.v. as a slow infusion over 20 min, and blood samples were collected at set intervals after the end of the infusion. The plasma concentrations of metronidazole and its main metabolite hydroxy-metronidazole were quantified by reversed-phase h.p.l.c. with u.v. detection. The metronidazole and hydroxy-metronidazole areas under the curve from 0 to 24 h (AUC0,24h), the metronidazole terminal elimination half-life (t1/2), the total clearance (CL), the metronidazole volume of distribution (V) values and the hydroxy-metronidazole/metronidazole concentration ratios as a function of time were calculated for each group. Comparison of the metronidazole AUC0,24h, t1/2 and CL values revealed that metronidazole metabolism is progressively impaired as the severity of liver disease increases. There were no variations in these parameters between the schistosomic and Child-Pugh A groups. In addition, there were no differences in the V and hydroxy-metronidazole AUC0,24h among the various groups studied. However, metronidazole metabolism was delayed in patients with hepatic disease, as illustrated by the hydroxy-metronidazole/metronidazole ratio 10 min after the end of metronidazole infusion. These results indicate that the clinical assessment of liver disease is paralleled by an impairment of metronidazole metabolism. Of the studied variables, we propose the hydroxy-metronidazole/metronidazole ratio 10 min after metronidazole infusion as a suitable and practical index for liver function evaluation. PMID:8703652

  15. Formulation, In Vitro and In Vivo Pharmacokinetics of Anti-HIV Vaginal Bioadhesive Gel

    PubMed Central

    Chatterjee, A; Bhowmik, B B; Thakur, Y S

    2011-01-01

    Inexpensive and female-controlled pre-exposure prophylaxis strategies to prevent mucosal transmission of the virus, is urgently needed with the rising prevalence of human immunodeficiency virus (HIV-1 and HIV2) infections in women. Zidovudine-loaded bioadhesive vaginal gel may become one of the very useful strategies, as it can be used not only for controlled release but also for enhancing bioavailability. Drug delivery through vaginal gel is a promising area for continued research with the aim of achieving controlled release with enhanced bioavailability over longer periods of time. The aim of the study was to develop a newer prolong releasing Zidovudine (AZT) bioadhesive vaginal gel to treat HIV infections with increased patient convenience. AZT-loaded bioadhesive vaginal gel was prepared successfully by using cold mechanical method. F3 formulation containing carbopol–HPMC (1:3) was selected and evaluated in order to achieve objectives of this study. In vitro drug release study of F3 showed in 24 h drug released following case I Fickian (n ≤ 0.5) transport mechanism, and in vivo drug release was found much better (Tmax), (Cmax), and bioavailability (F) comparison with oral pour drug solution. It was also showed good extrudability, spreadability, and bioadhesive strength. A generalized protocol, for the further research, in this area will surely expected to yield significant outcome with improved drug delivery system. PMID:21731351

  16. Dual-crosslinked oxidized, methacrylated alginate/PEG hydrogels for bioadhesive applications

    PubMed Central

    Jeon, Oju; Samorezov, Julia E.; Alsberg, Eben

    2013-01-01

    A degradable, cytocompatible bioadhesive can facilitate surgical procedures and minimize patient pain and postsurgical complications. In this study, a bioadhesive hydrogel system based on oxidized, methacrylated alginate/8-arm poly(ethylene glycol) amine (OMA/PEG) has been developed, and the bioadhesive characteristics of the crosslinked OMA/PEG hydrogels are evaluated. Here, we demonstrate that the swelling behavior, degradation profiles, and storage moduli of crosslinked OMA/PEG hydrogels are tunable by varying the degree of alginate oxidation. The crosslinked OMA/PEG hydrogels exhibit cytocompatibility when cultured with human bone marrow-derived mesenchymal stem cells. In addition, the adhesion strength of these hydrogels, controllable by varying the alginate oxidation level and measured using a porcine skin model, is superior to commercially available fibrin glue. This OMA/PEG hydrogel system with controllable biodegradation and mechanical properties and adhesion strength may be a promising bioadhesive for clinical use in biomedical applications, such as drug delivery, wound closure and healing, biomedical device implantation, and tissue engineering. PMID:24035886

  17. Tuning model drug release and soft-tissue bioadhesion of polyester films by plasma post-treatment.

    PubMed

    Mogal, Vishal T; Yin, Chaw Su; O'Rorke, Richard; Boujday, Souhir; Méthivier, Christophe; Venkatraman, Subbu S; Steele, Terry W J

    2014-04-23

    Plasma treatments are investigated as a post-production method of tuning drug release and bioadhesion of poly(lactic-co-glycolic acid) (PLGA) thin films. PLGA films were treated under varying conditions by controlling gas flow rate, composition, treatment time, and radio frequency (RF) power. In vitro release of the drug-like molecule fluorescein diacetate (FDAc) from plasma-treated PLGA was tunable by controlling RF power; an increase of 65% cumulative release is reported compared to controls. Bioadhesion was sensitive to RF power and treatment time, assessed using ex vivo shear-stress tests with wetted swine aorta. We report a maximum bioadhesion ∼6-fold that of controls and 5-fold that of DOPA-based mussel adhesives tested to swine skin.1 The novelty of this post-treatment is the activation of a hydrophobic polyester film for bioadhesion, which can be quenched, while simultaneously tuning drug-release kinetics. This exemplifies the promise of plasma post-treatment for in-clinic bioadhesive activation, along with technological advancements, i.e., atmospheric plasma and hand-held "plasma pencils". PMID:24666261

  18. Moxifloxacin in situ gelling microparticles-bioadhesive delivery system.

    PubMed

    Guo, Qiongyu; Aly, Ahmed; Schein, Oliver; Trexler, Morgana M; Elisseeff, Jennifer H

    2012-01-01

    Antibiotic use for ocular treatments has been largely limited by poor local bioavailability with conventional eyedrops formulations. Here, we developed a controlled delivery system composed of moxifloxacin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulated in a chondroitin sulfate-based, two-component bioadhesive hydrogel. Using a simple and fast electrohydrodynamic spray drying (electrospraying) technique, surfactant-free moxifloxacin-loaded microparticles were fabricated with diameters on the order of 1 μm. A mixed solvent system of methanol/dichloromethane (MeOH/DCM) was employed to prepare the microparticles for the electrospraying processing. Extended release of moxifloxacin using a series of MeOH/DCM mixed solvents was accomplished over 10 days with release concentrations higher than the minimum inhibitory concentration (MIC). In contrast, moxifloxacin loaded directly in hydrogels was released rapidly within 24 h. We observed a decrease of the drug release rate from the microparticles when using an increased percentage of methanol in the mixed solvent from 10% to 30% (v/v), which can be explained by the mixed solvent system providing a driving force to form a gradient of the drug concentrations inside the microparticles. In addition, the delivery system developed in this study, which incorporates a bioadhesive to localize drug release by in situ gelling, may potentially integrate antibiotic prophylaxis and wound healing in the eye. PMID:25755996

  19. Moxifloxacin in situ gelling microparticles–bioadhesive delivery system

    PubMed Central

    Guo, Qiongyu; Aly, Ahmed; Schein, Oliver; Trexler, Morgana M.; Elisseeff, Jennifer H.

    2012-01-01

    Antibiotic use for ocular treatments has been largely limited by poor local bioavailability with conventional eyedrops formulations. Here, we developed a controlled delivery system composed of moxifloxacin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulated in a chondroitin sulfate-based, two-component bioadhesive hydrogel. Using a simple and fast electrohydrodynamic spray drying (electrospraying) technique, surfactant-free moxifloxacin-loaded microparticles were fabricated with diameters on the order of 1 μm. A mixed solvent system of methanol/dichloromethane (MeOH/DCM) was employed to prepare the microparticles for the electrospraying processing. Extended release of moxifloxacin using a series of MeOH/DCM mixed solvents was accomplished over 10 days with release concentrations higher than the minimum inhibitory concentration (MIC). In contrast, moxifloxacin loaded directly in hydrogels was released rapidly within 24 h. We observed a decrease of the drug release rate from the microparticles when using an increased percentage of methanol in the mixed solvent from 10% to 30% (v/v), which can be explained by the mixed solvent system providing a driving force to form a gradient of the drug concentrations inside the microparticles. In addition, the delivery system developed in this study, which incorporates a bioadhesive to localize drug release by in situ gelling, may potentially integrate antibiotic prophylaxis and wound healing in the eye. PMID:25755996

  20. Metronidazole. A therapeutic review and update.

    PubMed

    Freeman, C D; Klutman, N E; Lamp, K C

    1997-11-01

    The nitroimidazole antibiotic metronidazole has a limited spectrum of activity that encompasses various protozoans and most Gram-negative and Gram-positive anaerobic bacteria. Metronidazole has activity against protozoans like Entamoeba histolytica, Giardia lamblia and Trichomonas vaginalis, for which the drug was first approved as an effective treatment. Anaerobic bacteria which are typically sensitive are primarily Gram-negative anaerobes belonging to the Bacteroides and Fusobacterium spp. Gram-positive anaerobes such as peptostreptococci and Clostridia spp. are likely to test sensitive to metronidazole, but resistant isolates are probably encountered with greater frequency than with the Gram-negative anaerobes. Gardnerella vaginalis is a pleomorphic Gram-variable bacterial bacillus that is also susceptible to metronidazole. Helicobacter pylori has been strongly associated with gastritis and duodenal ulcers. Classic regimens for eradicating this pathogen have included metronidazole, usually with acid suppression medication plus bismuth and amoxicillin. The activity of metronidazole against anaerobic bowel flora has been used for prophylaxis and treatment of patients with Crohn's disease who might develop an infectious complication. Treatment of Clostridium difficile-induced pseudomembraneous colitis has usually been with oral metronidazole or vancomycin, but the lower cost and similar efficacy of metronidazole, coupled with the increased concern about imprudent use of vancomycin leading to increased resistance in enterococci, have made metronidazole the preferred agent here. Metronidazole has played an important role in anaerobic-related infections. Advantages to using metronidazole are the percentage of sensitive Gram-negative anaerobes, its availability as oral and intravenous dosage forms, its rapid bacterial killing, its good tissue penetration, its considerably lower chance of inducing C. difficile colitis, and expense. Metronidazole has notable

  1. An investigation and characterization on alginate hydogel dressing loaded with metronidazole prepared by combined inotropic gelation and freeze-thawing cycles for controlled release.

    PubMed

    Sarheed, Omar; Rasool, Bazigha K Abdul; Abu-Gharbieh, Eman; Aziz, Uday Sajad

    2015-06-01

    The purpose of this study was to investigate the effect of combined Ca(2+) cross-linking and freeze-thawing cycle method on metronidazole (model drug) drug release and prepare a wound film dressing with improved swelling property. The hydrogel films were prepared with sodium alginate (SA) using the freeze-thawing method alone or in combination with ionotropic gelation with CaCl2. The gel properties such as morphology, swelling, film thickness, and content uniformity and in vitro dissolution profiles using Franz diffusion cell were investigated. The cross-linking process was confirmed by differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. In vitro protein adsorption test, in vivo wound-healing test, and histopathology were also performed. The hydrogel (F2) composed of 6% sodium alginate and 1% metronidazole prepared by combined Ca(2+) cross-linking and freeze-thawing cycles showed good swelling. This will help to provide moist environment at the wound site. With the in vivo wound-healing and histological studies, F2 was found to improve the wound-healing effect compared with the hydrogel without the drug, and the conventional product. PMID:25425388

  2. Formulation and Characterization of Cetylpyridinium Chloride Bioadhesive Tablets

    PubMed Central

    Akbari, Jafar; Saeedi, Majid; Morteza-Semnani, Katayoun; Kelidari, Hamidreza; Lashkari, Maryam

    2014-01-01

    Purpose: Bioadhesive polymers play an important role in biomedical and drug delivery applications. The aim of this study is to develop a sustained- release tablet for local application of Cetylpyridinium Chloride (CPC). This delivery system would supply the drug at an effective level for a long period of time, and thereby overcome the problem of the short retention time of CPC and could be used for buccal delivery as a topical anti-infective agent. Methods: CPC bioadhesive tablets were directly prepared using 7 mm flat-faced punches on a hydraulic press. The materials for each tablet were weighted, introduced into the die and compacted at constant compression pressure. The dissolution tests were performed to the rotation paddle method and the bioadhesive strength of the tablets were measured. Results: The results showed that as the concentration of polymer increased, the drug release rate was decreased. Also the type and ratio of polymers altered the release kinetic of Cetylpyridinium Chloride from investigated tablets. The bioadhesion strength increased with increasing the concentration of polymer and maximum bioadhesion strength was observed with HPMC K100M. Conclusion: The selected formulation of CPC bioadhesive tablet can be used as a suitable preparation for continuous release of CPC with appropriate bioadhesion strength. PMID:25436196

  3. PEG-Biscyanoacrylate Crosslinker for Octyl Cyanoacrylate Bioadhesive.

    PubMed

    Basu, Arijit; Veprinsky-Zuzulia, Ilana; Levinman, Mira; Barkan, Yoav; Golenser, Jacob; Domb, Abraham J

    2016-02-01

    PEG400 (polyethylene glycol, MW 400) biscyanoacrylate is synthesized and copolymerized with 2-octyl cyanoacrylate for potential use as bioadhesive. PEG400 biscyanoacrylate is synthesized from the esterification of anthracenyl cyanoacrylic acid where the anthracene unit serves as vinyl-protecting group. Copolymerization increases the plasticity, mechanical strength, and resilience of the resulted polymer as determined by dynamic mechanical analysis. Peeling test confirms its superior bioadhesive properties. Surface morphology is characterized by SEM imaging. The formulations are cytocompatible and safe. This cyanoacrylate composition may provide improved bioadhesive cyanoacrylates. PMID:26572088

  4. A Phase 3, Multicenter, Randomized, Double-Blind, Vehicle-Controlled Study Evaluating the Safety and Efficacy of Metronidazole Vaginal Gel 1.3% in the Treatment of Bacterial Vaginosis

    PubMed Central

    Schwebke, Jane R.; Marrazzo, Jeanne; Beelen, Andrew P.; Sobel, Jack D.

    2015-01-01

    Background Bacterial vaginosis (BV), a prevalent infection in women of reproductive age, is associated with increased risk of upper genital tract and sexually transmitted infections, and complications in pregnancy. Currently approved treatments include metronidazole, which requires once or twice daily intravaginal administration for 5 days or twice daily oral administration for 7 days. This phase 3 study determined the safety and efficacy of single-dose metronidazole vaginal gel (MVG) 1.3%. Methods In this double-blind, vehicle-controlled study, 651 women with clinical diagnosis of BV were randomized 1:1 to receive MVG 1.3% or vehicle vaginal gel. Primary efficacy measure was clinical cure (normal discharge, negative “whiff test,” and <20% clue cells) at day 21. Secondary measures included therapeutic cure (both clinical and bacteriological; day 21) and bacteriologic cure (Nugent score <4), clinical cure, and time to resolution of symptoms (day 7). Results A total of 487 participants were included in the primary analysis. Clinical and therapeutic cure rates (day 21) were higher in participants treated with MVG 1.3% compared with vehicle gel (37.2% vs. 26.6% [P = 0.010] and 16.8% vs. 7.2% [P = 0.001], respectively). Clinical and bacteriologic cure rates (day 7) were also higher in the MVG 1.3% group (46.0% vs. 20.0% [P < 0.001] and 32.7% vs. 6.3% [P < 0.001], respectively). The median time to resolution of symptoms was shorter in the MVG 1.3% (day 6) than vehicle group (not reached). No serious adverse events were reported, and incidence was similar across treatment groups. Conclusions Single-dose MVG 1.3% was safe and superior to vehicle gel in producing cure among women with BV. PMID:26222750

  5. Studies on the development of oral colon targeted drug delivery systems for metronidazole in the treatment of amoebiasis.

    PubMed

    Krishnaiah, Y S R; Bhaskar Reddy, P R; Satyanarayana, V; Karthikeyan, R S

    2002-04-01

    The aim of the present study is to develop colon targeted drug delivery systems for metronidazole using guar gum as a carrier. Matrix, multilayer and compression coated tablets of metronidazole containing various proportions of guar gum were prepared. All the formulations were evaluated for the hardness, drug content uniformity, and were subjected to in vitro drug release studies. The amount of metronidazole released from tablets at different time intervals was estimated by high performance liquid chromatography method. Matrix tablets and multilayer tablets of metronidazole released 43-52% and 25-44% of the metronidazole, respectively, in the physiological environment of stomach and small intestine depending on the proportion of guar gum used in the formulation. Both the formulations failed to control the drug release within 5 h of the dissolution study in the physiological environment of stomach and small intestine. The compression coated formulations released less than 1% of metronidazole in the physiological environment of stomach and small intestine. When the dissolution study was continued in simulated colonic fluids, the compression coated tablet with 275 mg of guar gum coat released another 61% of metronidazole after degradation by colonic bacteria at the end of 24 h of the dissolution study. The compression coated tablets with 350 and 435 mg of guar gum coat released about 45 and 20% of metronidazole, respectively, in simulated colonic fluids indicating the susceptibility of the guar gum formulations to the rat caecal contents. The results of the study show that compression coated metronidazole tablets with either 275 or 350 mg of guar gum coat is most likely to provide targeting of metronidazole for local action in the colon owing to its minimal release of the drug in the first 5 h. The metronidazole compression coated tablets showed no change either in physical appearance, drug content or in dissolution pattern after storage at 40 degrees C/75% RH for 6

  6. Possible nephotoxic interaction of lithium and metronidazole

    SciTech Connect

    Teicher, M.H.; Altesman, R.I.; Cole, J.O.; Schatzberg, A.F.

    1987-06-26

    Several classes of drugs can promote renal retention of lithium and, occasionally, can induce lithium intoxication. The antimicrobial agent metronidazole hydrochloride (Flagyl I.V.) was also implicated in producing such a reaction in one woman. The authors describe two patients who experienced toxic reactions to lithium following brief use of metronidazole. However, in these two patients, in contrast to the previous case, the degree of acute intoxication was less severe and treatment with metronidazole was completed without apparent suspicion, but persistent signs of renal damage later emerged.

  7. Treatment of human Demodex folliculorum by camphor oil and metronidazole.

    PubMed

    El-Shazly, Atef M; Hassan, Ashraf A; Soliman, Mohamed; Morsy, Gaza H; Morsy, Tosson A

    2004-04-01

    A total of 15 females suffering from erythematotelangiectatic rosacea and 12 females free from other dermatological lesions were selected. Demodex folliculorum infestation density in both patients and control were evaluated by non-invasive skin surface biopsies. Five facial sites were selected. The daily topical application of 1/3 diluted camphor oil with glycerol and 500 mg metronidazole orally were given for fifteen days. The results were very successful with no clinical side effects. PMID:15125520

  8. Effect of bioadhesion on initial in vitro buoyancy of effervescent floating matrix tablets of ciprofloxacin HCL

    PubMed Central

    Negi, Jeetendra Singh; Trivedi, Abhinav; Khanduri, Praveen; Negi, Vandana; Kasliwal, Nikhil

    2011-01-01

    The purpose of this study was to investigate effect of bioadhesion on the initial in vitro buoyancy behaviour of effervescent matrix tablets of ciprofloxacin HCl (CIPRO). Tablets were prepared by direct compression using HPMC K4M and Carbopol 971P as hydrophilic-controlled release polymers, sodium bicarbonate (NaHCO3) as gas-generating agent, polyplasdone XL, Explotab and Ac-Di-Sol as swelling agents. Tablets were evaluated for normal and modified initial in vitro floating behavior, floating duration, swelling behavior and in vitro drug release studies. A modified buoyancy lag time for tablets was determined in order to include the effect of bioadhesion on initial buoyancy. The initial buoyancy was found depended on bioadhesion ability of tablets. The lowest modified buoyancy lag time of 20 seconds was obtained for Formulation F7 having both NaHCO3 and polyplasdone XL. The floating duration was also found dependent on concentration of NaHCO3 and swelling agents. The drug release of F7 was also sustained up to 12-hr duration with anomalous drug transport mechanism. PMID:22171304

  9. A sunblock based on bioadhesive nanoparticles.

    PubMed

    Deng, Yang; Ediriwickrema, Asiri; Yang, Fan; Lewis, Julia; Girardi, Michael; Saltzman, W Mark

    2015-12-01

    The majority of commercial sunblock preparations use organic or inorganic ultraviolet (UV) filters. Despite protecting against cutaneous phototoxicity, direct cellular exposure to UV filters has raised a variety of health concerns. Here, we show that the encapsulation of padimate O (PO)--a model UV filter--in bioadhesive nanoparticles (BNPs) prevents epidermal cellular exposure to UV filters while enhancing UV protection. BNPs are readily suspended in water, facilitate adherence to the stratum corneum without subsequent intra-epidermal or follicular penetration, and their interaction with skin is water resistant yet the particles can be removed via active towel drying. Although the sunblock based on BNPs contained less than 5 wt% of the UV-filter concentration found in commercial standards, the anti-UV effect was comparable when tested in two murine models. Moreover, the BNP-based sunblock significantly reduced double-stranded DNA breaks when compared with a commercial sunscreen formulation. PMID:26413985

  10. A sunblock based on bioadhesive nanoparticles

    NASA Astrophysics Data System (ADS)

    Deng, Yang; Ediriwickrema, Asiri; Yang, Fan; Lewis, Julia; Girardi, Michael; Saltzman, W. Mark

    2015-12-01

    The majority of commercial sunblock preparations use organic or inorganic ultraviolet (UV) filters. Despite protecting against cutaneous phototoxicity, direct cellular exposure to UV filters has raised a variety of health concerns. Here, we show that the encapsulation of padimate O (PO)--a model UV filter--in bioadhesive nanoparticles (BNPs) prevents epidermal cellular exposure to UV filters while enhancing UV protection. BNPs are readily suspended in water, facilitate adherence to the stratum corneum without subsequent intra-epidermal or follicular penetration, and their interaction with skin is water resistant yet the particles can be removed via active towel drying. Although the sunblock based on BNPs contained less than 5 wt% of the UV-filter concentration found in commercial standards, the anti-UV effect was comparable when tested in two murine models. Moreover, the BNP-based sunblock significantly reduced double-stranded DNA breaks when compared with a commercial sunscreen formulation.

  11. A Sunblock Based On Bioadhesive Nanoparticles

    PubMed Central

    Deng, Yang; Ediriwickrema, Asiri; Yang, Fan; Lewis, Julia; Girardi, Michael

    2015-01-01

    The majority of commercial sunblock preparations utilize organic or inorganic ultraviolet (UV) filters. Despite protecting against cutaneous phototoxicity, direct cellular exposure to UV filters has raised a variety of health concerns. Here, we show that the encapsulation of padimate O (PO) - a model UV filter - in bioadhesive nanoparticles (BNPs) prevents epidermal cellular exposure to UV filters while enhancing UV protection. BNPs are readily suspended in water, facilitate adherence to the stratum corneum without subsequent intra-epidermal or follicular penetration, and their interaction with skin is water-resistant yet the particles can be removed via active towel drying. Although the sunblock based on BNPs contained less than 5 wt% of the UV-filter concentration found in commercial standards, the anti-UV effect was comparable when tested in two murine models. Moreover, the BNP-based sunblock significantly reduced double-stranded DNA breaks when compared to a commercial sunscreen formulation. PMID:26413985

  12. Muco-bioadhesive containing ginger officinale extract in the management of recurrent aphthous stomatitis: A randomized clinical study

    PubMed Central

    Haghpanah, Parya; Moghadamnia, Ali Akbar; Zarghami, Amin; Motallebnejad, Mina

    2015-01-01

    Background: Recurrent aphthous stomatitis (RAS) is the most common oral mucosal lesions in the general population. Various treatment modalities have been used; but no specific therapy proved to be definitive. Ginger Officinale (ginger) indicated to have anti-inflammatory properties in herbal medicine. Thus, this study aimed to evaluate the efficacy of ginger containing bioadhesive in the treatment of aphthous ulcers. Methods: In this randomized double-blind placebo-controlled trial, 15 patients were enrolled. The clinical efficacy of the mucoadhessive on pain, inflammatory zone and ulcer's diameter in the test period was compared with that of the base treatment and no treatment periods during 10 days of study. Results: Significant reduction in pain was observed on day 5 between placebo (using base bioadhesives) and without treatment periods at the first phase of the study (4.53 vs. 3.27; P=0.038. ( Reduction in inflamed halo diameters was significant on day 1 between without treatment and ginger containing bioadhesives )46.73 vs 28.67; P=0.044). Other variables such as the diameter of ulcers did not indicate any significant differences in both periods. Conclusion: This study indicated that ginger bioadhesive is capable to relieve pain of RAS. However, its efficacy on ulcer diameter, inflamed halo and healing time was not significantly different compared to the results of the placebo received period. PMID:26221489

  13. Electrochemical Determination of Metronidazole in Tablet Samples Using Carbon Paste Electrode

    PubMed Central

    Nikodimos, Yosef

    2016-01-01

    Cyclic voltammetric investigation of metronidazole at carbon paste electrode revealed an irreversible reduction peak centered at about −0.4 V. Observed peak potential shift with pH in the range 2.0 to 8.5 indicated the involvement of protons during the reduction of metronidazole, whereas the peak potential shift with scan rate in the range 10–250 mV/s confirmed the irreversibility of the reduction reaction. A better correlation coefficient for the dependence of peak current on the scan rate than on the square root of scan rate indicated an adsorption controlled kinetics. Under the optimized method and solution parameters, an excellent linearity between the reductive peak current and the concentration of metronidazole was observed in the concentration range 1.0 × 10−6 to 5.0 × 10−4 M with a correlation coefficient, method detection limit (based on s = 3σ), and limit of quantification of 0.999, 2.97 × 10−7 M and 9.91 × 10−7 M, respectively. Good recovery results for spiked metronidazole in tablet samples and selective determination of metronidazole in tablet formulations in the presence of selected potential interferents such as rabeprazole, omeprazole, and tinidazole confirmed the potential applicability of the developed method for the determination of metronidazole in real samples like pharmaceutical tablets. PMID:27119041

  14. Effect of HPMC and mannitol on drug release and bioadhesion behavior of buccal discs of buspirone hydrochloride: In-vitro and in-vivo pharmacokinetic studies

    PubMed Central

    Jaipal, A.; Pandey, M.M.; Charde, S.Y.; Raut, P.P.; Prasanth, K.V.; Prasad, R.G.

    2014-01-01

    Delivery of orally compromised therapeutic drug molecules to the systemic circulation via buccal route has gained a significant interest in recent past. Bioadhesive polymers play a major role in designing such buccal dosage forms, as they help in adhesion of designed delivery system to mucosal membrane and also prolong release of drug from delivery system. In the present study, HPMC (release retarding polymer) and mannitol (diluent and pore former) were used to prepare bioadhesive and controlled release buccal discs of buspirone hydrochloride (BS) by direct compression method. Compatibility of BS with various excipients used during the study was assessed using DSC and FTIR techniques. Effect of mannitol and HPMC on drug release and bioadhesive strength was studied using a 32 factorial design. The drug release rate from delivery system decreased with increasing levels of HPMC in formulations. However, bioadhesive strength of formulations increased with increasing proportion of HPMC in buccal discs. Increased levels of mannitol resulted in faster rate of drug release and rapid in vitro uptake of water due to the formation of channels in the matrix. Pharmacokinetic studies of designed bioadhesive buccal discs in rabbits demonstrated a 10-fold increase in bioavailability in comparison with oral bioavailability of buspirone reported. PMID:26106280

  15. Effect of HPMC and mannitol on drug release and bioadhesion behavior of buccal discs of buspirone hydrochloride: In-vitro and in-vivo pharmacokinetic studies.

    PubMed

    Jaipal, A; Pandey, M M; Charde, S Y; Raut, P P; Prasanth, K V; Prasad, R G

    2015-07-01

    Delivery of orally compromised therapeutic drug molecules to the systemic circulation via buccal route has gained a significant interest in recent past. Bioadhesive polymers play a major role in designing such buccal dosage forms, as they help in adhesion of designed delivery system to mucosal membrane and also prolong release of drug from delivery system. In the present study, HPMC (release retarding polymer) and mannitol (diluent and pore former) were used to prepare bioadhesive and controlled release buccal discs of buspirone hydrochloride (BS) by direct compression method. Compatibility of BS with various excipients used during the study was assessed using DSC and FTIR techniques. Effect of mannitol and HPMC on drug release and bioadhesive strength was studied using a 3(2) factorial design. The drug release rate from delivery system decreased with increasing levels of HPMC in formulations. However, bioadhesive strength of formulations increased with increasing proportion of HPMC in buccal discs. Increased levels of mannitol resulted in faster rate of drug release and rapid in vitro uptake of water due to the formation of channels in the matrix. Pharmacokinetic studies of designed bioadhesive buccal discs in rabbits demonstrated a 10-fold increase in bioavailability in comparison with oral bioavailability of buspirone reported. PMID:26106280

  16. Montmorillonite nanodevices for the colon metronidazole delivery.

    PubMed

    Calabrese, Ilaria; Cavallaro, Gennara; Scialabba, Cinzia; Licciardi, Mariano; Merli, Marcello; Sciascia, Luciana; Turco Liveri, Maria Liria

    2013-11-30

    The adsorption profiles of the antibiotic metronidazole (MNE) into the K10-montmorillonite (MMT-K10) clay and the subsequent release have been investigated as a function of pH and MNE/MMT-K10 ratio, in order to evaluate the potential of the MNE/MMT-K10 hybrids as controlled drug delivery system. The adsorption mechanism has been first elucidated by performing complementary equilibrium and kinetic studies and through the X-ray diffractometry (XRD) characterization of the obtained composite materials. The gathered results allowed us to propose a mechanism consisting of a multi-step pathway involving the neutral and the cationic form of the drug, which interact with different sites of the clay surfaces, i.e. the interlayer region and the faces of the lamella. In a second step the drug release kinetics has been studied under physiological pH mimicking conditions simulating the oral drug administration and delivery. For the sake of comparison the commercial formulation has also been employed for the release studies. The investigation of the release profiles and the comparison with the commercial formulation of the drug reveal that the new-tailor made formulation could be fruitful exploited for successfully prolonged the action of drug in the desired site. PMID:24076230

  17. Development of Injectable Citrate-Based Bioadhesive Bone Implants

    PubMed Central

    Xie, Denghui; Guo, Jinshan; Mehdizadeh, Mohammadreza; Tran, Richard T.; Chen, Ruisong; Sun, Dawei; Qian, Guoying; Jin, Dadi; Bai, Xiaochun; Yang, Jian

    2014-01-01

    Injectable bone implants have been widely used in bone tissue repairs including the treatment of comminuted bone fractures (CBF). However, most injectable bone implants are not suitable for the treatment of CBF due to their weak tissue adhesion strengths and minimal osteoinduction. Citrate has been recently reported to promote bone formation through enhanced bioceramic integration and osteoinductivity. Herein, a novel injectable citrate-based mussel-inspired bioadhesive hydroxyapatite (iCMBA/HA) bone substitute was developed for CBF treatment. iCMBA/HA can be set within 2–4 minutes and the as-prepared (wet) iCMBA/HA possess low swelling ratios, compressive mechanical strengths of up to 3.2±0.27 MPa, complete degradation in 30 days, suitable biocompatibility, and osteoinductivity. This is also the first time to demonstrate that citrate supplementation in osteogenic medium and citrate released from iCMBA/HA degradation can promote the mineralization of osteoblastic committed human mesenchymal stem cells (hMSCs). In vivo evaluation of iCMBA/HA in a rabbit comminuted radial fracture model showed significantly increased bone formation with markedly enhanced three-point bending strength compared to the negative control. Neovascularization and bone ingrowth as well as highly organized bone formation were also observed showing the potential of iCMBA/HA in treating CBF. PMID:25580247

  18. Acute Onset Sensory Polyneuropathy Due to Metronidazole Therapy.

    PubMed

    Singh, Jitendra; Atam, Virendra; Dinkar, Anju

    2015-09-01

    Metronidazole is associated with numerous neurologic complications, including peripheral neuropathy particularly in patients; those are on high doses of metronidazole for prolonged period. We hereby report a case of liver abscess that developed sensory polyneuropathy following 11 days of metronidazole therapy at low cumulative dose. PMID:27608880

  19. The effect of topical metronidazole therapy on experimentally-induced periodontitis in the beagle dog.

    PubMed

    Klinge, B; Kuvatanasuhati, J; Attström, R; Kalfas, S; Edwardsson, S

    1992-10-01

    The present study was performed to assess the effect of topical metronidazole therapy on ligature-induced periodontitis in beagle dogs. 6 beagle dogs with experimentally-induced periodontitis on the mandibular 2nd, 3rd and 4th premolars were treated with metronidazole 10% dental paste 2 x daily for 4 weeks in an open placebo-controlled study using a split-mouth design. Recordings of probing pocket depth, bleeding on probing and gingival index were performed before commencement of treatment and repeated weekly during the 4-weeks treatment period. Concurrently, samples for microbiological analysis were collected from 2 of the dogs. The results demonstrated that probing pocket depth, bleeding on probing and gingival index had improved significantly in the metronidazole-treated side compared with the placebo-treated side. Black pigmented Bacteroides spp. and Spirochetes, present in all samples before treatment, were eliminated from the metronidazole-treated side after the 1st week of treatment and throughout the treatment period, whereas they were present in all samples from the placebo-treated side. The result of the present study demonstrates that topical application of metronidazole in a dental paste, improves the clinical features of the experimentally-induced periodontitis and eliminates some of the micro-organisms associated with the disease. PMID:1447390

  20. Evaluation of metronidazole-loaded poly(3-hydroxybutyrate) membranes to potential application in periodontitis treatment.

    PubMed

    da Silva, Marcio A C; Oliveira, Renata N; Mendonça, Roberta Helena; Lourenço, Talita G B; Colombo, Ana Paula V; Tanaka, Marcelo N; Tude, Elena M O; da Costa, Marysilvia F; Thiré, Rossana Mara S M

    2016-01-01

    Guided tissue regeneration is a technique used for periodontium reconstruction. This technique uses barrier membranes, which prevent epithelial growth in the wound site and may also be used to release antibiotics, to protect the wound against opportunistic infections. Periodontal poly(3-hydroxybutyrate) membranes containing metronidazole (a drug used to help in infection control) were produced and characterized. The kinetic mechanism of the metronidazole delivery of leached and nonleached membrane as well as its cytotoxicity and structural integrity were evaluated. Poly(3-hydroxybutyrate) membranes containing 0.5-2 wt % of the drug and 20 wt % of the plasticizer were manufactured via compression molding. Based on morphological analysis, membranes loaded with 2% metronidazole were considered for detailed studies. The results revealed that metronidazole delivery by the leached membranes seemed to follow the Fick's law. Membranes were noncytotoxic. The amount of metronidazole delivered was in the range of the minimal inhibitory concentration for Porphyromonas gingivalis, and the membranes inhibited the proliferation of these bacteria. Besides, they maintained their mechanical resistance after 30 days of immersion in phosphate buffer at pH 7.4. PMID:25655488

  1. Efficacy and Safety of Ceftazidime-Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-abdominal Infection: Results From a Randomized, Controlled, Double-Blind, Phase 3 Program

    PubMed Central

    Mazuski, John E.; Gasink, Leanne B.; Armstrong, Jon; Broadhurst, Helen; Stone, Greg G.; Rank, Douglas; Llorens, Lily; Newell, Paul; Pachl, Jan

    2016-01-01

    Background. When combined with ceftazidime, the novel non–β-lactam β-lactamase inhibitor avibactam provides a carbapenem alternative against multidrug-resistant infections. Efficacy and safety of ceftazidime-avibactam plus metronidazole were compared with meropenem in 1066 men and women with complicated intra-abdominal infections from 2 identical, randomized, double-blind phase 3 studies (NCT01499290 and NCT01500239). Methods. The primary end point was clinical cure at test-of-cure visit 28–35 days after randomization, assessed by noninferiority of ceftazidime-avibactam plus metronidazole to meropenem in the microbiologically modified intention-to-treat (mMITT) population (in accordance with US Food and Drug Administration guidance), and the modified intention-to-treat and clinically evaluable populations (European Medicines Agency guidance). Noninferiority was considered met if the lower limit of the 95% confidence interval for between-group difference was greater than the prespecified noninferiority margin of −12.5%. Results. Ceftazidime-avibactam plus metronidazole was noninferior to meropenem across all primary analysis populations. Clinical cure rates with ceftazidime-avibactam plus metronidazole and meropenem, respectively, were as follows: mMITT population, 81.6% and 85.1% (between-group difference, −3.5%; 95% confidence interval −8.64 to 1.58); modified intention-to-treat, 82.5% and 84.9% (−2.4%; −6.90 to 2.10); and clinically evaluable, 91.7% and 92.5% (−0.8%; −4.61 to 2.89). The clinical cure rate with ceftazidime-avibactam plus metronidazole for ceftazidime-resistant infections was comparable to that with meropenem (mMITT population, 83.0% and 85.9%, respectively) and similar to the regimen's own efficacy against ceftazidime-susceptible infections (82.0%). Adverse events were similar between groups. Conclusions. Ceftazidime-avibactam plus metronidazole was noninferior to meropenem in the treatment of complicated intra

  2. Metronidazole-triazole conjugates: Activity against Clostridium difficile and parasites

    PubMed Central

    Jarrad, Angie M.; Karoli, Tomislav; Debnath, Anjan; Tay, Chin Yen; Huang, Johnny X.; Kaeslin, Geraldine; Elliott, Alysha G.; Miyamoto, Yukiko; Ramu, Soumya; Kavanagh, Angela M.; Zuegg, Johannes; Eckmann, Lars; Blaskovich, Mark A.T.; Cooper, Matthew A.

    2015-01-01

    Metronidazole has been used clinically for over 50 years as an antiparasitic and broad-spectrum antibacterial agent effective against anaerobic bacteria. However resistance to metronidazole in parasites and bacteria has been reported, and improved second-generation metronidazole analogues are needed. The copper catalysed Huigsen azide-alkyne 1,3-dipolar cycloaddition offers a way to efficiently assemble new libraries of metronidazole analogues. Several new metronidazole-triazole conjugates (Mtz-triazoles) have been identified with excellent broad spectrum antimicrobial and antiparasitic activity targeting Clostridium difficile, Entamoeba histolytica and Giardia lamblia. Cross resistance to metronidazole was observed against stable metronidazole resistant C. difficile and G. lamblia strains. However for the most potent Mtz-triazoles, the activity remained in a therapeutically relevant window. PMID:26117821

  3. Characterization of spray dried bioadhesive metformin microparticles for oromucosal administration.

    PubMed

    Sander, Camilla; Madsen, Katrine Dragsbæk; Hyrup, Birgitte; Nielsen, Hanne Mørck; Rantanen, Jukka; Jacobsen, Jette

    2013-11-01

    Delivery of drugs into or via the oral cavity offers some distinct advantages due to the easy access to the oral mucosa, fast onset of action, and avoidance of hepatic and intestinal degradation mechanisms. To overcome the effective removal mechanisms existing in this area, bioadhesive drug delivery systems are considered a promising approach as they facilitate a close contact between the drug and the oral mucosa. In this study, bioadhesive chitosan-based microparticles of metformin hydrochloride were prepared by spray drying aqueous dispersions with different chitosan:metformin ratios and chitosan grades with increasing molecular weights. A recently developed ex vivo flow retention model with porcine buccal mucosa was used to evaluate the bioadhesive properties of spray dried microparticles. An important outcome of this study was that microparticles with the desired metformin content could be prepared and analyzed using the ex vivo retention model. We observed an increase in metformin retention on porcine mucosa with increasing chitosan:metformin ratios, while no effect of increasing the chitosan molecular weight was found. Rheological characterization of feeds for spray drying was performed and used for designing the microparticles. This way, novel microparticles with similar particle size distribution, high encapsulation efficiencies, and low moisture content were obtained independent of the chitosan:metformin ratio and the chitosan molecular weight. In conclusion, chitosan:metformin microparticles with significant bioadhesive properties on porcine buccal mucosa were developed. PMID:23774184

  4. A randomised multicentre study to compare the safety and efficacy of albendazole and metronidazole in the treatment of giardiasis in children.

    PubMed

    Dutta, A K; Phadke, M A; Bagade, A C; Joshi, V; Gazder, A; Biswas, T K; Gill, H H; Jagota, S C

    1994-01-01

    A randomised control multicentre study to compare the safety and efficacy of albendazole and metronidazole in the treatment of giardiasis in children is reported. One hundred and fifty children of either sex (age range: 2-10 years) were randomised to receive either a single dose of 400 mg of albendazole suspension, or 22.5 mg/kg/day of metronidazole in 3 divided doses for 5 consecutive days. At the end of therapy, majority of children in both treatment groups were symptom free. Two days after completion of therapy, 97% of children in both treatment groups were giardia free in the stools. Side effects were noted in 3 children in the albendazole group, and in 20 children in the metronidazole group. We conclude that albendazole suspension is as effective as metronidazole in the treatment of giardial infection in children. It is safe and has fewer side effects as compared to metronidazole. PMID:7721374

  5. Investigation of the physicochemical and physicomechanical properties of a novel intravaginal bioadhesive polymeric device in the pig model.

    PubMed

    Ndesendo, Valence M K; Pillay, Viness; Choonara, Yahya E; du Toit, Lisa C; Buchmann, Eckhart; Meyer, Leith C R; Khan, Riaz A; Rosin, Uwe

    2010-06-01

    The purpose of this study was to develop and evaluate the bioadhesivity, in vitro drug release, and permeation of an intravaginal bioadhesive polymeric device (IBPD) loaded with 3'-azido-3'-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Modified polyamide 6,10, poly(lactic-coglycolic acid), polyacrylic acid, polyvinyl alcohol, and ethylcellulose were blended with model drugs AZT and PSS as well as radio-opaque barium sulfate (BaSO4) and then compressed into caplet devices on a tableting press. One set of devices was coated with 2% w/v pentaerythritol polyacrylic acid (APE-PAA) while another remained uncoated. Thermal analysis was performed on the constituent polymers as well the IBPD. The changes in micro-environmental pH within the simulated human vaginal fluid due to the presence of the IBPD were assessed over a period of 30 days. Textural profile analysis indicated that the bioadhesivity of the APE-PAA-coated devices (3.699 +/- 0.464 N; 0.0098 +/- 0.0004 J) was higher than that of the uncoated devices (1.198 +/- 0.150 N; 0.0019 +/- 0.0001 J). In addition, BaSO4-facilitated X-ray imaging revealed that the IBPD adhered to pig vaginal tissue over the experimental period of 30 days. Controlled drug release kinetics was obtained over 72 days. During a 24-h permeation study, an increase in drug flux for both AZT (0.84 mg cm(-2) h(-1)) and PSS (0.72 mg cm(-2) h(-1)) was realized up to 12 h and thereafter a steady-state was achieved. The diffusion and dissolution dynamics were mechanistically deduced based on a chemometric and molecular structure modeling approach. Overall, results suggested that the IBPD may be sufficiently bioadhesive with desirable physicochemical and physicomechanical stability for use as a prolonged intravaginal drug delivery device. PMID:20446071

  6. Intra-gastric performance and bioavailability study of a new per-oral bioadhesive Verapamil HCl matrix tablet in dogs.

    PubMed

    Yassin, Alaa Eldeen B; Alkhaled, F; al-Suwayeh, S; Elkheshen, S

    2003-09-01

    In a previous study, we developed a per-oral extended--release bioadhesive matrix tablet for verapamil HCl (VP). The system combined both strong bioadhesion and sustained release properties in vitro. The purpose of this study is to evaluate the in vivo performance of the prepared bioadhesive tablets (B). The conduction of a periodic X-ray imaging of the abdomen of beagle dogs, after administration of B containing 12% barium sulfate, was used to evaluate the intra-gastric performance. The VP concentrations in blood samples taken at specified times after oral administration of B to fasted beagle dogs were determined and compared with those obtained after administration of a commercial sustained release VP tablets (Manidon 120 R). The X-ray images showed that bioadhesive tablets remained almost at the same place in the stomach for at least 6 hours while it disappeared after 1 hour in case of the control tablets. No statistical difference was seen between the Cmax, tmax, AUC, t1/2, and MRT for B compared to Manidon. The Cmax was found to be 51.4 +/- 15.5 and 48.6 +/- 17.9 (ng/ml) for Manidon and B, respectively and the corresponding tmax were 7.0 +/- 1.9 and 6.0 +/- 0, respectively. The AUCO-. for Manidon and B were 949.84 +/- 245.11 and 722.92 +/- 144.42 ng.h/ml, respectively. So, the prepared B tablets can be considered bioequivalent to the commercial Manidon Retard product. PMID:14677272

  7. Development of Bioadhesive Chitosan Superporous Hydrogel Composite Particles Based Intestinal Drug Delivery System

    PubMed Central

    Modhia, Ishan; Mehta, Anant; Patel, Rupal; Patel, Chhagan

    2013-01-01

    Bioadhesive superporous hydrogel composite (SPHC) particles were developed for an intestinal delivery of metoprolol succinate and characterized for density, porosity, swelling, morphology, and bioadhesion studies. Chitosan and HPMC were used as bioadhesive and release retardant polymers, respectively. A 32 full factorial design was applied to optimize the concentration of chitosan and HPMC. The drug loaded bioadhesive SPHC particles were filled in capsule, and the capsule was coated with cellulose acetate phthalate and evaluated for drug content, in vitro drug release, and stability studies. To ascertain the drug release kinetics, the drug release profiles were fitted for mathematical models. The prepared system remains bioadhesive up to eight hours in intestine and showed Hixson-Crowell release with anomalous nonfickian type of drug transport. The application of SPHC polymer particles as a biomaterial carrier opens a new insight into bioadhesive drug delivery system and could be a future platform for other molecules for intestinal delivery. PMID:23984380

  8. What would we do without metronidazole?

    PubMed

    Stover, Kayla R; Riche, Daniel M; Gandy, Christie L; Henderson, Harold

    2012-04-01

    Metronidazole is a treatment of choice for several types of infections, but coexisting conditions or concomitant medications may preclude its use. Although tinidazole, a newer nitroimidazole, may be an option in cases where drug interactions make the use of metronidazole inadvisable, similar absolute contraindications exist. In situations where nitroimidazole use is contraindicated or inadvisable, clinicians may have difficulty deciding on efficacious treatment options. For the treatment of trichomoniasis, alternatives include furazolidone, clotrimazole, nonoxynol-9 or paromomycin. Alternatives for bacterial vaginosis include clindamycin topically or systemically. For giardiasis, alternative options include paromomycin, nitazoxanide or the antihelminthic benzimidazoles. Alternatives for Clostridium difficile are varied, including oral vancomycin, nitazoxanide and rifaximin. Although options are limited, alternative therapies for treatment of patients with absolute contraindications to the nitroimidazole antibiotics are available. PMID:21817887

  9. Research on the development of bioadhesive vaginal tablets containing 5-fluorouracil.

    PubMed

    Cojocaru, Ileana; Palade, Laura; Popovici, Iuliana; Georgescu, Gabriela; Bîrsan, Magdalena

    2013-01-01

    Biomucoadhesive vaginal tablets are modern formulations used in current therapy to achieve controlled release of the active substance at the application site by maintaining the pharmaceutical preparation at that level. This can be achieved by using mucoadhesive substances with different mechanical and physical-chemical properties. Two cellulose derivatives of different viscosity, Metolose 90 SH 4000 and Metolose 90 SH 100000, and two types of polyacrylates with different cross linking degrees, Carbopol 71, low degree of cross linking, and Carbopol 974, high degree of cross linking were used. In a previous study twelve original formulations of bioadhesive vaginal tablets containing 100 mg 5-fluorouracil (5-FU)/tablet (F1-F12) were formulated, prepared and analyzed. The pharmacotechnical characterization of the bioadhesive vaginal tablets containing 5-FU was performed by determining their specific quality characteristics. For the optimization of formulations, the influence of formulation factors on some quality characteristics (mechanical strength, friability, disintegration time) which may be influenced by the nature and amount of auxiliary substances used was studied by SPSS statistical software and statistical analysis ANOVA tests. The results are in favor of formulations F1, F2 containing 20-30% Carbopol 71 and of 37-47% Microcelac. PMID:24505926

  10. Comparative study of the mechanical behaviour of a cyanoacrylate and a bioadhesive.

    PubMed

    García Páez, J M; Jorge Herrero, E; Rocha, A; Maestro, M; Castillo-Olivares, J L; Millan, I; Carrera Sanmartin, A; Cordon, A

    2004-02-01

    We compared the mechanical resistance of 18 samples of calf pericardium bonded with a 100 mm2 overlap, by two types of glues: a cyanoacrylate (Loctite 4011) and a bioadhesive (BioGlue). Comparative tensile testing was also carried out in 40 paired samples, 20 bonded with the cyanoacrylate and 20 unbonded controls. The findings at rupture showed a greater resistance of the calf pericardium glued with cyanoacrylate, with a mean tensile strength of 0.15 MPa vs. 0.04 MPa for the biological glue (p= 0.000). They also demonstrated a loss of resistance of the samples bonded with cyanoacrylate when compared with that of the unbonded other halves of the pairs: 0.20 MPa and 0.27 MPa vs. 19.47 MPa and 24.44 MPa (p < 0.001). The method of selection by means of paired samples made it possible to establish the equations that relate the stress and strain, or deformation, with excellent coefficients of determination (R2). These equations demonstrate the marked elastic behaviour of the bonded samples. Moreover, these findings show the cyanoacrylate to be superior to the biological glue, leading to the examination of the compatibility, inalterability over time and mechanical behaviour of the cyanoacrylate in sutured samples, as well as the study of the anisotropy of the biomaterial when bonded with a bioadhesive. PMID:15330043

  11. A Bioadhesive Nanoparticle-Hydrogel Hybrid System for Localized Antimicrobial Drug Delivery.

    PubMed

    Zhang, Yue; Zhang, Jianhua; Chen, Maggie; Gong, Hua; Thamphiwatana, Soracha; Eckmann, Lars; Gao, Weiwei; Zhang, Liangfang

    2016-07-20

    Effective antibacterial treatment at the infection site associated with high shear forces remains challenging, owing largely to the lack of durably adhesive and safe delivery platforms that can enable localized antibiotic accumulation against bacterial colonization. Inspired by delivery systems mimicking marine mussels for adhesion, herein, we developed a bioadhesive nanoparticle-hydrogel hybrid (NP-gel) to enhance localized antimicrobial drug delivery. Antibiotics were loaded into polymeric nanoparticles and then embedded into a 3D hydrogel network that confers adhesion to biological surfaces. The combination of two distinct delivery platforms, namely, nanoparticles and hydrogel, allows the hydrogel network properties to be independently tailored for adhesion while maintaining controlled and prolonged antibiotic release profile from the nanoparticles. The bioadhesive NP-gel developed here showed superior adhesion and antibiotic retention under high shear stress on a bacterial film, a mammalian cell monolayer, and mouse skin tissue. Under a flow environment, the NP-gel inhibited the formation of an Escherichia coli bacterial film. When applied on mouse skin tissue for 7 consecutive days, the NP-gel did not generate any observable skin reaction or toxicity, implying its potential as a safe and effective local delivery platform against microbial infections. PMID:27352845

  12. Treatment of Clostridium difficile infection in mice with vancomycin alone is as effective as treatment with vancomycin and metronidazole in combination

    PubMed Central

    Erikstrup, Lise Tornvig; Aarup, Mie; Hagemann-Madsen, Rikke; Dagnaes-Hansen, Frederik; Kristensen, Brian; Olsen, Katharina Elisabeth Pribil; Fuursted, Kurt

    2015-01-01

    Objective Clostridium difficile is a major cause of nosocomial infectious diarrhoea. Treatment of C. difficile infection (CDI) depends on disease severity. A combination of vancomycin and metronidazole is often recommended in severe cases. The aim of this study was to examine, in a murine model of CDI, if mice treated with a combination of vancomycin and metronidazole had a better clinical outcome than mice treated with vancomycin or metronidazole alone. Design C57BL/6J mice pretreated with an antimicrobial mixture were challenged with C. difficile VPI 10463 or phosphate-buffered saline by oral gavage. After the challenge, the mice were treated with placebo, vancomycin, metronidazole or a combination of vancomycin and metronidazole for 10 days. The mice were monitored for 20 days with weight and a clinical score. Stool samples were examined for C. difficile spore load and presence of C. difficile toxins. Results None of the mice in the vancomycin-treated group died during the treatment phase compared to a mortality of 17%, 33% and 55% in the combination, metronidazole and infected control group, respectively. Mice treated with vancomycin alone or in combination with metronidazole recovered from CDI faster than mice treated with metronidazole alone. However, after discontinuation of treatment, vancomycin-treated and combination-treated mice succumbed to clinical and bacteriological relapse. Conclusions Mice treated with vancomycin alone had a better clinical outcome in the treatment phase of CDI than mice treated with metronidazole alone. A combination of vancomycin and metronidazole did not improve the clinical outcome when compared to treatment with vancomycin alone. Trial registration number The trial registration number from the Danish Experimental Animal Inspectorate is J number 2012-15-2934-00422. PMID:26568840

  13. Metronidazole-induced alterations in murine spermatozoa morphology.

    PubMed

    Mudry, Marta D; Palermo, Ana M; Merani, María S; Carballo, Marta A

    2007-02-01

    The aim of this work was to assess the effect of metronidazole (MTZ) on the stages of the seminiferous epithelial cycle and spermatozoa morphology when the drug is administered in human therapeutic doses to 60-day-old CFW male mice. The frequency of the stages was established by counting spermatocytes in pachytene and spermatids. Abnormalities in the flagellum or the head, lack of maturity and multiple malformations, were considered in the morphological analysis. Murine control strain was compared with MTZ treated group (v.ip 130 mg/kg/bw) both kept in standard captivity conditions. Cellular composition or number of stages in the seminiferous tubules were not altered in MTZ exposed animals, though the number of cells in stages I, V and XII was increased. The sperm cell morphology was severely affected by the treatment with potentially serious consequences on the normal fertilization process. Thus, the MTZ has to be considered as a conceivable thread regarding male fertility. PMID:17184970

  14. Nanostructured materials for ocular delivery: nanodesign for enhanced bioadhesion, transepithelial permeability and sustained delivery

    PubMed Central

    Kim, Jean; Schlesinger, Erica B; Desai, Tejal A

    2016-01-01

    Effective drug delivery to the eye is an ongoing challenge due to poor patient compliance coupled with numerous physiological barriers. Eye drops for the front of the eye and ocular injections for the back of the eye are the most prevalent delivery methods, both of which require relatively frequent administration and are burdensome to the patient. Novel drug delivery techniques stand to drastically improve safety, efficacy and patient compliance for ocular therapeutics. Remarkable advances in nanofabrication technologies make the application of nanostructured materials to ocular drug delivery possible. This article focuses on the use of nanostructured materials with nanoporosity or nanotopography for ocular delivery. Specifically, we discuss nanotopography for enhanced bioadhesion and permeation and nanoporous materials for controlled release drug delivery. As examples, application of polymeric nanostructures for greater transepithelial permeability, nanostructured microparticles for enhanced preocular retention time and nanoporous membranes for tuning drug release profile are covered. PMID:26652282

  15. Development of Bioadhesive Transdermal Bupivacaine Gels for Enhanced Local Anesthetic Action

    PubMed Central

    Cho, Cheong-Weon; Kim, Deok-Bae; Shin, Sang-Chul

    2012-01-01

    Topical drug dosage forms such as ointments and creams can be easily removed through wetting, movement and contact. The new bioadhesive formulations with enhanced local anesthetic effects are needed for topical administration. The adhesive capacity of hydroxypropyl methylcellulose (HPMC) was determined by measuring the maximum detachment force and the adhesion work with an auto peeling tester. The release of drug from a HPMC gel was studied according to the drug concentration. Permeation study through the rat skin was performed at 37°C using phosphate buffer solution (pH = 7.4) as a receptor medium. To increase the skin permeation of bupivacaine from the HPMC gels, penetration enhancer such as the saturated and unsaturated fatty acids, the pyrrolidones, the propylene glycol derivatives, the glycerides, and the non-ionic surfactants were incorporated in the bupivacaine-HPMC gels. The local anesthetic effect of the formulated gel preparation was examined using a tail-flick analgesimeter. As the concentration of HPMC increased, the bioadhesive force and viscosity were increased. The rate of drug release was increased with increasing the drug concentration. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the most enhancing effects on drug permeation through the skin. In the rat tail flick test, the area under the efficacy curve of bupivacaine gel containing polyoxyethylene 2-oleyl ether and tetrahydrozoline showed a 2.36-fold increase in anesthetic activity compared to control gel without any additives. The bupivacaine gels containing both penetration enhancer and vasoconstrictor showed enhancement and prolonged efficacy compared to the control gel. To enhance the local anesthetic effects of bupivacaine, the transdermal bupivacaine gel formulation containing penetration enhancer and vasoconstrictor could be developed. PMID:24250466

  16. Assemblies for in vitro measurement of bioadhesive strength and retention characteristics in simulated vaginal environment.

    PubMed

    Vermani, Kavita; Garg, Sanjay; Zaneveld, Lourens J D

    2002-10-01

    The vaginal route of administration offers a promising option for local and systemic delivery of drugs. Conventional vaginal formulations are associated with limitations of poor retention, leakage, and messiness, thereby causing inconvenience to users. To overcome these limitations, formulations that adhere to the vaginal mucosa for a sufficient period of time need to be developed. Bioadhesion and retention are desirable characteristics of a vaginal formulation to achieve desired efficacy. These properties can be built in during formulation development by the use of bioadhesive polymers. In the present study, assemblies for in vitro measurement of bioadhesive strength and retention characteristics of vaginal formulations have been developed. A modified simulated vaginal fluid (SVFM) was used to simulate vaginal conditions for bioadhesion studies. Cellophane hydrated with SVFM and isolated sheep vaginal mucosa were used as model membranes. The bioadhesive potential of various polymers and their combinations was evaluated. Among the polymers evaluated, xanthan gum (XG), sodium alginate (SA), Polycarbophil (PC), and their combinations (XG + SA and XG + PC) were found to possess significant bioadhesive strength. In retention experiments, XG, SA, and combinations (XG + SA and XG + PC) were retained in isolated sheep vaginal tissue, while PC exhibited poor retention under experimental conditions. Based on the results of the study conducted, XG, SA, and combinations (XG + SA and XG + PC) have been proposed as potential candidates for developing bioadhesive vaginal drug delivery systems. PMID:12455472

  17. Formulation and evaluation of atenolol floating bioadhesive system using optimized polymer blends

    PubMed Central

    Siddam, Haritha; Kotla, Niranjan G.; Maddiboyina, Balaji; Singh, Sima; Sunnapu, Omprakash; Kumar, Anil; Sharma, Dinesh

    2016-01-01

    Introduction: Oral sustained release gastro retentive dosage forms offer several advantages for drugs having absorption from the upper gastrointestinal tract to improve the bioavailability of medications which have narrow absorption window. The aim of the study was to develop a floating bioadhesive drug delivery system exhibiting a unique combination of floatation and bioadhesion to prolong the residence in the stomach using atenolol as a model drug. Methods: Prior to compression, polymeric blend(s) were evaluated for flow properties. The tablets were prepared by direct compression method using bioadhesive polymer like Carbopol 934P and hydrophilic polymers like HPMC K4M, HPMC K15M, and HPMC K100M. The prepared tablets were evaluated for physical characteristics, bioadhesive strength, buoyancy lag time, swelling index and in vitro drug release studies. Results: The mean bioadhesive strength was found to be in the range of 16.2 to 52.1 gm. The optimized blend (F11) showed 92.3% drug releases after 24 hrs. Whilst, increase in concentration of carbopol 934P, bioadhesive strength and swelling index was increased with slow release. The n values of optimized formulations were found in the range of 0.631-0.719 indicating non-fickian anomalous type transport mechanism. Conclusion: The study aided in developing an ideal once-a-day gastro retentive floating drug delivery system with improved floating, swelling and bioadhesive characteristics with better bioavailability. PMID:27051631

  18. A Raman spectroscopic investigation of bioadhesive tetracaine local anaesthetic formulations.

    PubMed

    Dennis, Andrew C; McGarvey, John J; Woolfson, A David; McCafferty, Dermot F; Moss, Gary P

    2004-07-26

    Raman spectroscopy at 785 nm has been employed to characterise the properties of tetracaine in bioadhesive gel and patch formulations. In the first study, interactions between the drug and excipients in novel bioadhesive patch systems were characterised. It was determined that the drug did not interact with any of its formulation components, and that this was an important factor in its clinical performance, particularly the rapid onset of anaesthesia. Investigations of drug uptake in the stratum corneum from a gel formulation suggested that tetracaine rapidly undergoes a phase-change upon application to the skin. The intensity of the tetracaine Raman bands at approximately 1600 cm(-1) suggests that the local anaesthetic is rapidly absorbed into the skin. Decreases in Raman tetracaine band intensities, along with an absence in the concomitant alteration in the internal standard spectra, indicates an decrease in the tetracaine concentration present in the gel. Further, a baseline indicating complete tetracaine absorption appears to be reached after approximately 40 min of exposure. After this time little further absorption was observed, suggesting that the stratum corneum "reservoir" was saturated with tetracaine at this time. This is consistent with the optimum application time required for tetracaine gels to attain maximum clinical efficacy. This study has indicated the effectiveness of Raman spectroscopy in the analysis of gel-based pharmaceutical preparations, showing it to be a simple, rapid, virtually non-invasive technique for determination of tetracaine. PMID:15234793

  19. Single-dose metronidazole clears Opalina sp. from juvenile Bufo woodhousii.

    PubMed

    Nickol, Devin R; Tufts, Danielle M

    2013-06-01

    Protozoans of the family Opalinidae are intestinal commensals in amphibians. To test the hypothesis that these organisms are susceptible to the antiprotozoal antibiotic metronidazole, we randomly assigned 60 juvenile Woodhouse's toads ( Bufo woodhousii ) to receive a single oral dose of metronidazole or water. In pilot trials, the prevalence of opalinids in untreated members of this population was over 70%. One-third of the study population was dissected at each of 3 time points: 18 hr, 1 wk, and 2 wk post-treatment. An examiner blinded to the toad's treatment history determined the presence or absence of opalinids using a dissecting microscope. Opalinids were found in 3/10 toads in the treatment group and 9/10 in the control group after 18 hr (P < 0.02), in none of the treatment group and 8/10 in the control group after 1 wk (P < 0.001), and in none of the treatment group and 10/10 in the control group after 2 wk (P < 0.0001). These results suggest that a single-dose of metronidazole quickly and reliably clears opalinids from juvenile Woodhouse's toads with no evidence of short-term recurrence. The treatment was well tolerated, with no apparent morbidity and no mortality in either group. Future exploration of opalinid-related host fitness consequences may be facilitated by this simple method of developing a protozoan-free host population. PMID:23339344

  20. Treatment of Infections Caused by Metronidazole-Resistant Trichomonas vaginalis

    PubMed Central

    Cudmore, Sarah L.; Delgaty, Kiera L.; Hayward-McClelland, Shannon F.; Petrin, Dino P.; Garber, Gary E.

    2004-01-01

    Infections with the sexually transmitted protozoan Trichomonas vaginalis are usually treated with metronidazole, a 5-nitroimidazole drug derived from the antibiotic azomycin. Metronidazole treatment is generally efficient in eliminating T. vaginalis infection and has a low risk of serious side effects. However, studies have shown that at least 5% of clinical cases of trichomoniasis are caused by parasites resistant to the drug. The lack of approved alternative therapies for T. vaginalis treatment means that higher and sometimes toxic doses of metronidazole are the only option for patients with resistant disease. Clearly, studies of the treatment and prevention of refractory trichomoniasis are essential. This review describes the mechanisms of metronidazole resistance in T. vaginalis and provides a summary of trichomonicidal and vaccine candidate drugs. PMID:15489348

  1. Successful treatment of refractory Trichomonas vaginalis infection using intravenous metronidazole.

    PubMed

    Hawkins, Isobel; Carne, Christopher; Sonnex, Christopher; Carmichael, Andrew

    2015-08-01

    Trichomonas vaginalis is a sexually transmitted protozoan infection resulting in a vulvo-vaginitis and altered vaginal discharge in symptomatic women. Since its introduction in the 1960 s, metronidazole has been the first-line drug for trichomonal infection. Other nitroimidazoles, such as tinidazole, are used as alternative regimens with similar activity but at a greater expense. Treatment failure usually represents patient non-compliance or reinfection, although metronidazole resistance has previously been documented. Sensitivity testing is currently not available in the UK. Patients with disease unresponsive to first-line treatments pose a major challenge, as therapeutic options are limited. This case looks at a patient with refractory disease over an 18-month period, where intravenous infusion of metronidazole resulted in cure after multiple previous therapy failures. There is limited evidence to endorse the use of intravenous metronidazole, and this case report provides further support for its efficacy. PMID:25161176

  2. Metronidazole Toxicity in Cockayne Syndrome: A Case Series.

    PubMed

    Wilson, Brian T; Strong, Andrew; O'Kelly, Sean; Munkley, Jennifer; Stark, Zornitza

    2015-09-01

    Cockayne syndrome (CS) is a rare genetic disorder characterized by small stature, intellectual disability, and accelerated pathologic aging. Through the Cockayne Syndrome Natural History Study, we have identified 8 cases of acute hepatic failure after metronidazole administration (8% of our cohort), 3 of which were fatal. The interval between initial administration and death was 6 to 11 days. Two of these patients also experienced acute neurologic deficit. Both hepatotoxicity and acute neurologic deficit have been reported previously as extremely rare adverse events after metronidazole administration. However, we have not identified any patients with CS who have received metronidazole without serious adverse effects. We recommend that a diagnosis of CS be considered an absolute contraindication to the use of metronidazole. PMID:26304821

  3. Spectrophotometric determination of metronidazole and secnidazole in pharmaceutical preparations.

    PubMed

    Saffaj, T; Charrouf, M; Abourriche, A; Abboud, Y; Bennamara, A; Berrada, M

    2004-10-01

    A rapid and sensitive spectrophotometric method is proposed for determination of metronidazole and secnidazole. The method depends on the reduction of metronidazole and secnidazole molecule with zinc dust and hydrochloric acid flowed by diazotization and coupling with 8-quinolinol to give red colored chromogens easily measured spectrophotometrically which has lambda(max) = 500 nm. The experimental conditions were optimized and Berr's law was obeyed over the applicable concentration ranges both techniques were applied successfully to a wide variety of pharmaceutical preparations. PMID:15474063

  4. Entamoeba histolytica and Trichomonas vaginalis: trophozoite growth inhibition by metronidazole electro-transferred water.

    PubMed

    Heredia-Rojas, J Antonio; Torres-Flores, Antonio Cayetano; Rodríguez-De la Fuente, Abraham O; Mata-Cárdenas, Benito David; Rodríguez-Flores, Laura E; Barrón-González, María Porfiria; Torres-Pantoja, Antonio Cayetano; Alcocer-González, Juan M

    2011-01-01

    The influence of low-frequency electromagnetic (LF-EM) waves on microorganisms has been a subject of experimental investigations for more than two decades and the results are promising. In parallel, an interesting procedure known as biophysical-information-therapy or bioresonance therapy (BRT) which in principle is based on LF-EM stimulation, has emerged. BRT was discovered in the late 1980's but it is still poorly studied. This paper demonstrates that by transferring metronidazole information to water samples by an electronic amplifier (BRT device), the growth of axenically cultured trophozoites of Entamoeba histolytica and Trichomonasvaginalis is significantly inhibited, compared with those cultures treated with non and sham electro-transferred water samples. A positive control of metronidazole, a well-known cytotoxic drug against parasites, was used as a reference. PMID:20603119

  5. Absence of Strand Breaks in Deoxyribonucleic Acid Treated with Metronidazole

    PubMed Central

    LaRusso, Nicholas F.; Tomasz, Maria; Kaplan, David; Müller, Miklós

    1978-01-01

    The deoxyribonucleic acid (DNA)-degrading potential of metronidazole was evaluated in vitro by three techniques: determination of melting curve, measurement of viscosity, and centrifugation in neutral or alkaline sucrose gradients. Studies were performed on calf thymus DNA and on 3H-labeled or unlabeled pneumococcal and T7 phage DNA after treatment with metronidazole alone or metronidazole reduced by sodium dithionite in the presence of DNA. This latter process is known to elicit covalent binding of metronidazole to DNA. Reduced or unreduced metronidazole had no effect on the melting properties, viscosity, or sedimentation velocity of the nucleic acids studied. Sodium dithionite alone, however, caused a 25% decrease in the intrinsic viscosity of pneumococcal DNA, and decreased the sedimentation velocity of pneumococcal and T7 phage DNA in both neutral and alkaline sucrose gradients. These data suggest that degradation of DNA is not important in the interaction of metronidazole with nucleic acids, an interaction assumed relevant to the cytotoxic, radiosensitizing, and mutagenic activities of this compound. PMID:626487

  6. Indirect electroreduction as pretreatment to enhance biodegradability of metronidazole.

    PubMed

    Saidi, I; Soutrel, I; Floner, D; Fourcade, F; Bellakhal, N; Amrane, A; Geneste, F

    2014-08-15

    The removal of metronidazole, a biorecalcitrant antibiotic, by coupling an electrochemical reduction with a biological treatment was examined. Electroreduction was performed in a home-made flow cell at -1.2V/SCE on graphite felt. After only one pass through the cell, analysis of the electrolyzed solution showed a total degradation of metronidazole. The biodegradability estimated from the BOD5/COD ratio increased from 0.07 to 0.2, namely below the value usually considered as the limit of biodegradability (0.4). In order to improve these results, indirect electrolysis of metronidazole was performed with a titanium complex known to reduce selectively nitro compounds into amine. The catalytic activity of the titanium complex towards electroreduction of metronidazole was shown by cyclic voltammetry analyses. Indirect electrolysis led to an improvement of the biodegradability from 0.07 to 0.42. To confirm the interest of indirect electroreduction to improve the electrochemical pretreatment, biological treatment was then carried out on activated sludge after direct and indirect electrolyses; different parameters were followed during the culture such as pH, TOC and metronidazole concentration. Both electrochemical processes led to a more efficient biodegradation of metronidazole compared with the single biological treatment, leading to an overall mineralization yield for the coupling process of 85%. PMID:24968253

  7. Metronidazole activation and isolation of Clostridium acetobutylicum electron transport genes.

    PubMed Central

    Santangelo, J D; Jones, D T; Woods, D R

    1991-01-01

    An Escherichia coli F19 recA, nitrate reductase-deficient mutant was constructed by transposon mutagenesis and shown to be resistant to metronidazole. This mutant was a most suitable host for the isolation of Clostridium acetobutylicum genes on recombinant plasmids, which activated metronidazole and rendered the E. coli F19 strain sensitive to metronidazole. Twenty-five E. coli F19 clones containing different recombinant plasmids were isolated and classified into five groups on the basis of their sensitivity to metronidazole. The clones were tested for nitrate reductase, pyruvate-ferredoxin oxidoreductase, and hydrogenase activities. DNA hybridization and restriction endonuclease mapping revealed that four of the C. acetobutylicum insert DNA fragments on recombinant plasmids were linked in an 11.1-kb chromosomal fragment. DNA sequencing and amino acid homology studies indicated that this DNA fragment contained a flavodoxin gene which encoded a protein of 160 amino acids that activated metronidazole and made the E. coli F19 mutant very sensitive to metronidazole. The flavodoxin and hydrogenase genes which are involved in electron transfer systems were linked on the 11.1-kb DNA fragment from C. acetobutylicum. Images PMID:1991710

  8. Effect of Metronidazole on Halitosis of 2 to 10 Years Old Children

    PubMed Central

    Sayedi, Sayed Javad; Modaresi, Mohammad Reza; Saneian, Hosein

    2015-01-01

    Background: Regarding the fact that halitosis has social and personal aspects which can lead to social embarrassment and consequently low self-esteem and self-confidence in subjects suffering from the problem, especially children, its proper treatment is an important issue. Objectives: The aim of this study was to evaluate the effect of metronidazole as a nonspecific antimicrobial agent in the treatment of halitosis in children. Materials and Methods: In this study, 2-10 years old children with oral halitosis were enrolled. Children without H. pylori infection and parasitic infection were randomized in two interventional and control groups. Metronidazole was given 5mg/kg/day for one week. Information regarding the demographic characteristics of studied population and halitosis (duration and time of day with more halitosis and its severity) before and after intervention was recorded using a questionnaire Results: 77 children with halitosis were studied in two interventional (40 children) and control (37 children) groups. There was no significant difference between two groups before intervention. After intervention, halitosis improvement rate - according to the reports of mothers of studied children - was higher significantly in intervention group (P < 0.05). Conclusions: The results support the effectiveness of metronidazole in the treatment of halitosis. Moreover, it supports recent findings regarding the participation of specific bacteria specially unculturable ones in the pathogenesis of the disease. PMID:26199692

  9. Injectable Citrate-Based Mussel-Inspired Tissue Bioadhesives With High Wet Strength for Sutureless Wound Closure

    PubMed Central

    Mehdizadeh, M. Reza; Weng, Hong; Gyawali, Dipendra; Tang, Liping; Yang, Jian

    2012-01-01

    The existing surgical adhesives are not ideal for wet tissue adhesion required in many surgeries such as those for internal organs. Developing surgical adhesives with strong wet tissue adhesion, controlled degradability and mechanical properties, and excellent biocompatibility has been a significant challenge. Herein, learning from nature, we report a one-step synthesis of a family of injectable citrate-based mussel-inspired bioadhesives (iCMBAs) for surgical use. Within the formulations investigated, iCMBAs showed 2.5–8.0 folds stronger wet tissue adhesion strength over the clinically used fibrin glue, demonstrated controlled degradability and tissue-like elastomeric mechanical properties, and exhibited excellent cyto/tissue-compatibility both in vitro and in vivo. iCMBAs were able to stop bleeding instantly and suturelessly, and close wounds (2 cm long × 0.5 cm deep) created on the back of Sprague-Dawley rats, which is impossible when using existing gold standard, fibrin glue, due to its weak wet tissue adhesion strength. Equally important, the new bioadhesives facilitate wound healing, and are completely degraded and absorbed without eliciting significant inflammatory response. Our results support that iCMBA technology is highly translational and could have broad impact on surgeries where surgical tissue adhesives, sealants, and hemostatic agents are used. PMID:22902057

  10. Double-blind, randomized pilot study of bioadhesive chlorhexidine gel in the prevention and treatment of mucositis induced by chemoradiotherapy of head and neck cancer

    PubMed Central

    Diaz-Sanchez, Rosa-Maria; Pachón-Ibáñez, Jerónimo; Marín-Conde, Fátima; Rodríguez-Caballero, Ángela; Gutierrez-Perez, Jose-Luis

    2015-01-01

    Background To evaluate, in an initial way, the effectiveness of bioadhesive chlorhexidine gel 0.2% versus placebo as a preventive and therapeutic intervention of oral mucositis induced by radiation therapy and chemotherapy in patients diagnosed with head and neck cancer treated with chemoradiotherapy. Material and Methods In this pilot study, 7 patients (range of age: 18- 65), having histological documented diagnosis of squamous carcinoma on the head and neck region in stage III and IV, and receiving combined radiation treatment and chemotherapy (cisplatin 100 mg/m2 IV on days 1, 22, and 43 of irradiation) were studied. Simultaneously, a topical application was performed with bioadhesive chlorhexidine gel 0.2% in the study group, and the placebo gel for the control group in 5 applications per day, from the time of initiation of cancer treatment to 2 weeks after completion of chemo-radiotherapy treatment (11 weeks of follow-up). The gradation of mucositis, pain, analgesic consumption, infectious complications, and treatment tolerance was measured. Results After 7 patients completed the protocol, any differences were observed between groups in an interval analysis. Mucositis, pain, and tolerance was similar in both groups. Conclusions Our results must be interpreted with caution due to the reduced sample size, but the use of bioadhesive chlorhexidine gel 0.2% didn’t contribute clinical improvement to the oral mucositis induced by radiation therapy and chemotherapy. Key words: Chlorhexidine, mucositis, head and neck cancer. PMID:25662553

  11. Vulvoperineal Crohn's disease: response to metronidazole.

    PubMed

    Khaled, Aida; Ezzine-Sebai, Nadia; Fazaa, Becima; Zeglaoui, Faten; Zermani, Rachida; Kamoun, Mohamed Ridha

    2010-01-01

    A 46-year-old woman with a medical history of chronic juvenile arthritis with bilateral prosthetic hips presented with vulvoperineal ulcerations of 3 years' duration. There was no diarrhea or recent weight loss. Cutaneous examination showed asymmetrical vulvar edema of the labia minora and labia majora with deep and linear ulcerations having verrucous borders located on the inguinocrural regions and the buttocks fold (Figure 1). On physical examination there was bilateral limited mobilization of the hips. A biopsy specimen was taken from the border of the vulvar ulceration and histologic examination showed under a hyperplasic epidermis an epithelioid granuloma with multinucleated giant cells of the dermis without caseification. Laboratory analyses and results from chest x-ray were normal. Results for Koch bacilla in the spittle, microbiologic studies (staining for microorganisms and cultures), and tuberculin intradermoreaction were negative. There was no Crohn's disease aspect on colonoscopy, and there was normal small bowel enterography. Systematic intestinal biopsies were also with normal aspect. Based on the clinical data and granulomatous histologic characteristics, the diagnosis of metastatic Crohn's disease without digestive involvement was obtained. The patient was started on metronidazole 1 g/d. After 6 months of treatment, there was an almost-complete healing of ulcerations (Figure 2). Treatment was well-tolerated. PMID:21137614

  12. Bioadhesive lozenge for the improved delivery of cetylpyridinium chloride.

    PubMed

    Collins, A E; Deasy, P B

    1990-02-01

    Conventional lozenges produce a high initial release of drug in the oral cavity, which rapidly declines to subtherapeutic levels, and requires multiple daily administration with associated problems of systemic toxicity and compliance. Various multilayer compacts containing cetylpyridinium chloride were evaluated in vitro using release into simulated saliva (buffer pH 6.6). The drug loading, the wax content of the active layer, and the composition of the bioadhesive layer were important variables affecting product performance. Following preliminary in vivo studies, the release of a three-layered device containing drug in a nonadhesive and flavored waxy exposed layer was studied in six humans using HPLC and was shown not to be affected by location within the mouth. In comparison with a proprietary lozenge formulation, the device produced more uniform and effective levels of drug (approximately 20 micrograms.mL-1), with adequate comfort, taste, and irritancy over a period of 3 h. PMID:2324958

  13. Bioadhesion to model thermally responsive surfaces

    NASA Astrophysics Data System (ADS)

    Andrzejewski, Brett Paul

    contrast possessed no adhesion to the pure component C11EG6OH SAM at both temperatures examined, 25 and 40°C. The protein adhesion data to the mixed SAM also supports the hypothesis that the mixed SAM displays a non-fouling molecular conformation at 25°C whereas it displays a dominantly fouling molecular conformation at 40°C. Advancing contact angles obtained through tensiometry were used to find the surface free energy of the mixed SAM before and after the thermal response using the van Oss-Good-Chaudhury method. The surface tension values obtained, 42 and 38 mN/m for 22 and 40°C, respectively, are not dissimilar enough with regard to error to make conclusions. In a similar manner, the surface free energy of another mixed SAM composed of alkyl and trimethylamine thiolates was also calculated. PNIPAAm brushes grown on a silicon substrate by atom-transfer radical polymerization (ATRP) were imaged by AFM and characterized by XPS. The height of the resulting brushes could be controlled from ˜5 to 55 nm by reaction time. A thermal response was observed for polymer brushes with a length greater than 20 nm. For polymer brush lengths greater than 20 nm, the static contact angle at 22°C was 35° and varied from 60 to 80° at 40°C. The thermal response was also observed using the captive bubble method. Force-distance curves of the PNIPAAm brushes were taken with an unmodified silicon nitride AFM cantilever at incremental temperature steps. At room temperature the force-distance data was fit to the Alexander-de Gennes model resulting in a hydrated polymer length of 235 nm. The Young's modulus was calculated using the Hertz model and changed from ˜80 MPa at 26°C to ˜350 MPa at 40°C. The solvent condition of the Alexander-de Gennes model was set to the case of good solvent and showed close match to the force-distance data at 26°C. The match was not as close when the solvent condition was set to theta solvent condition and compared to the force-distance data at 40

  14. Metronidazole Decreases Viability of DLD-1 Colorectal Cancer Cell Line

    PubMed Central

    Sadowska, Anna; Krętowski, Rafał; Szynaka, Beata; Cechowska-Pasko, Marzanna

    2013-01-01

    Abstract The aim of our study was to evaluate the impact of metronidazole (MTZ) on DLD-1 colorectal cancer cell (CRC) line. Toxicity of MTZ was determined by MTT test. Cells were incubated with MTZ used in different concentrations for 24, 48, and 72 hours. The effect of MTZ on DNA synthesis was measured as [3H]-thymidine incorporation. The morphological changes in human DLD-1 cell line were defined by transmission electron microscope OPTON 900. The influence of MTZ on the apoptosis of DLD-1 cell lines was detected by flow cytometry and fluorescence microscopy, while cell concentration, volume, and diameter were displayed by Scepter Cell Counter from Millipore. Our results show that cell viability was diminished in all experimental groups in comparison with the control, and the differences were statistically significant. We did not find any significant differences in [3H]-thymidine incorporation in all experimental groups and times of observation. Cytofluorimetric assays demonstrated a statistically significant increase of apoptotic rate in MTZ concentrations 10 and 50 μg/mL after 24 hours; 0.1, 10, 50, and 250 μg/mL after 48 hours; and in all concentrations after 72 hours compared with control groups. In the ultrastructural studies, necrotic or apoptotic cells were occasionally seen. In conclusion, MTZ affects human CRC cell line viability. The reduction of cell viability was consistent with the apoptotic test. PMID:23777253

  15. Effect of Plasma Pretreatments on the Bio-adhesive Functionalized by Biomimetic Catechol Groups to Human Dentin

    NASA Astrophysics Data System (ADS)

    Lee, Sangbae; Kim, Kwangmahn; Kim, Kyoungnam

    2012-10-01

    Plasma pretreatments have been introduced for modifying the surface chemistry of biomaterials. In an effort to improve the strength of the human dentin/bio-adhesive joint, oxygen plasma pretreatments to the bio-adhesive were investigated. Plasma treatments were carried out using custom-built and low pressure. Dentin were treated with plasma and used to prepare lap shear tests. Bio-adhesives were prepared synthesizing dopamine methacrylamide (DMA) monomer. DMA were copolymerized with 2-methoxyethylacrylate (MEA) by free radical polymerization. Proton nuclear magnetic resonance (^1H-NMR) and Gel permeation chromatography (GPC) analysis on samples of synthesized p(DMA-co-MEA) was performed to confirm that the resulting materials had the desired chemical structure. The effects of plasma pretreatments on surface chemistry were studied using Fourier transform infrared analysis (FTIR), and contact angle measurements. Oxygen plasma pretreatments enhanced adhesive strength by oxidizing of the catechol residue and creating a cross-linking as compared with control group. Furthermore plasma pretreatments lead to increase hydrophilicity of copolymers. Prospectively, the great potential of advanced technology in creation of the ``Plasma pretreatment to the DOPA adhesives'' would lead to the development of versatile method for coating to medial devices as well as dentin bonding.

  16. Use of a chondroitin sulfate bioadhesive to enhance integration of bioglass particles for repairing critical-size bone defects.

    PubMed

    Yang, Shuqing; Guo, Qiongyu; Shores, Lucas S; Aly, Ahmed; Ramakrishnan, Meera; Kim, Ga Hye; Lu, Qiaozhi; Su, Lixin; Elisseeff, Jennifer H

    2015-01-01

    Replacement of autogenous or allograft bones by artificial graft materials represents a growing area of interest in current bone repair strategies. Bioactive ceramics in particulate form, such as Bioglass (BG) 45S5, stimulate bone mineralization comparable to autologous bone grafts, but have potential issues of particle migration and inflammation. The aim of this study was to employ a chondroitin sulfate- (CS-) based bioadhesive to improve integration of the bioglass (NovaBone Putty) to prevent particle migration and promote bone regeneration. This BG-CS composite can encapsulate bone marrow (BM) to form a mechanically stable construct, BG-CS-BM. Rheological characterization confirmed the formation of CS-BM hydrogel by reacting the CS-based bioadhesive with the BM. Compared to the bioglass, the BG-CS-BM composite demonstrated a superior capacity to maintain construct integrity under both aqueous and turbulent environments in vitro. After implantation for 4 weeks in a critical-size distal femoral bone defect in a rabbit model, there was significantly greater bone growth in BG-CS-BM as compared to bioglass-only and the empty control. Unlike BG-CS-BM, BG-CS recruited BM in situ from the bone defect. BG-CS demonstrated a similar effect in bone formation but at a comparatively slower rate than BG-CS-BM over 6-weeks' implantation. PMID:24616321

  17. Metronidazole pharmacokinetics in patients with acute renal failure.

    PubMed

    Somogyi, A A; Kong, C B; Gurr, F W; Sabto, J; Spicer, W J; McLean, A J

    1984-02-01

    The pharmacokinetics and metabolism of intravenous metronidazole were studied in six patients with acute renal failure. In two of the patients a single dose (500 mg) of metronidazole was administered, whereas in four patients the steady-state pharmacokinetics were studied after four days therapy of 500 mg twice daily. Plasma concentrations of metronidazole and its hydroxy and acetic acid metabolites were measured by a specific and sensitive HPLC method. The volume of distribution was 0.65 +/- 0.13 l/kg (mean +/- S.D.), elimination half-life was 9.9 +/- 2.5 h and total plasma clearance was 55.5 +/- 17.7 ml/min. Renal clearance was almost non-existent (1.4 +/- 1.4 ml/min), whereas non-renal clearance was 54.0 +/- 18.2 ml/min. Steady-state plasma concentrations of metronidazole were 15.3 +/- 3.8 mg/l, the hydroxy metabolite were 17.4 +/- 2.0 mg/l and the acetic acid metabolite were 1.2 +/- 0.8 mg/l. In the patients studied, a dosing regimen of 500 mg twice daily resulted in therapeutically adequate blood levels of metronidazole. PMID:6706889

  18. Inhibition of nitrogenase activity by metronidazole in rhodopseudomonas capsulata.

    PubMed

    Kelley, B C; Nicholas, D J

    1981-07-01

    Inhibition of photosynthetic growth of Rhodopseudomonas capsulata by metronidazole was dependent on the nitrogen supply in culture solutions. Cultures fixing dinitrogen were more susceptible to inhibition by low concentrations than those supplied with NH4+. Light-dependent C2H2 reduction and H2 production by washed cells were inhibited by 80% and 60% respectively by 1 mM metronidazole. When this compound was first reduced with H2-palladised asbestos prior to assay, it only partially restricted C2H2 reduction in washed cells (33%) compared with unreduced inhibitor (68%). Metronidazole was without effect on other metabolic functions. Thus, even at 40 mM it did not inhibit either (a) dark or light respiration in cells grown under photo- and chemo-heterotrophic conditions; (b) H2-dependent photoreduction of 14CO2; (C) gamma-glutamyltransferase activity of glutamine synthetase in cell-free extracts (25 mM inhibitor). Metronidazole (1 mM) completely inhibited C2H2 reduction by washed cells of Azotobacter vinelandii. The dithionite-dependent C2H2 reduction of a partially purified nitrogenase was only partially inhibited (30%) by 1 mM metronidazole. PMID:6116482

  19. A comparative clinical trial of albendazole versus metronidazole in giardiasis.

    PubMed

    Misra, P K; Kumar, A; Agarwal, V; Jagota, S C

    1995-03-01

    The adverse effects and treatment failures to some of the currently recommended drugs for giardia infection have given rise to the need for alternative antigiardial agents. In an open, randomized parallel group study, the safety and efficacy of albendazole was compared with that of metronidazole for the treatment of giardiasis in children. Sixty two children aged between 2-12 years were randomized to receive either albendazole suspension 400 mg daily for 5 days or metronidazole suspension 7.5 mg/kg thrice daily for 5 days. The mean days required for cure, as evident by absence of cysts and/or trophozoites in the stool specimen, was 3.7 + 1.4 and 4.5 + 1.1 days, respectively for children on albendazole and metronidazole therapy. Six children on metronidazole therapy developed anorexia 2 to 4 days after the treatment. Albendazole proved as effective as metronidazole in the treatment of giardia infection in children with the added advantage of absence of anorexia. PMID:8613282

  20. [Antimicrobial therapy with nitroheterocyclic compounds, for example, metronidazole and nitrofurantoin].

    PubMed

    Hof, H

    1988-12-01

    Nitroheterocyclic compounds, such as metronidazole and nitrofurantoin, are widely used in medical practice for the treatment of infectious diseases. Indeed, they exhibit a strong antimicrobial effect, which is directed not only against several groups of bacteria but also against certain protozoa and even worms. The nitrogroup coupled onto a heterocyclic structure, for example an imidazole, a thiazole or a furan ring, represents the proper site of effect. A priori the nitrogroup is, however, inactive. It has to be activated by microbial nitroreductases after penetration into the microbial cell. Those microorganisms which possess an anaerobic metabolism exhibit marked nitroreductase activity. The intracellularly produced intermediate products attack the chromosomal DNA of the target cell. Consequently, diverse mutations may occur. Partially, these chromosomal damages can be compensated by an SOS repair mechanism, which is under the control of the uvrB, lexA and polA genes. SOS repair-deficient mutants are much more susceptible to nitrocompounds than repair-proficient strains. Principally, the genotoxic activity of nitrocontaining compounds can also be expressed in eukaryotic cells of human or animal origin. This virtual property does not, however, prohibit clinical use, since until now no evidence of increased cancer incidence has been observed after rational therapy with nitrocompounds. PMID:3061931

  1. Discriminative Dissolution Method for Benzoyl Metronidazole Oral Suspension.

    PubMed

    da Silva, Aline Santos; da Rosa Silva, Carlos Eduardo; Paula, Fávero Reisdorfer; da Silva, Fabiana Ernestina Barcellos

    2016-06-01

    A dissolution method for benzoyl metronidazole (BMZ) oral suspensions was developed and validated using a high-performance liquid chromatography (HPLC) method. After determination of sink conditions, dissolution profiles were evaluated using different dissolution media and agitation speeds. The sample insertion mode in dissolution media was also evaluated. The best conditions were obtained using a paddle, 50 rpm stirring speed, simulated gastric fluid (without pepsin) as the dissolution medium, and sample insertion by a syringe. These conditions were suitable for providing sink conditions and discriminatory power between different formulations. Through the tested conditions, the results can be considered specific, linear, precise, accurate, and robust. The dissolution profiles of five samples were compared using the similarity factor (f 2) and dissolution efficiency. The dissolution kinetics were evaluated and described by the Weibull model. Whereas there is no monograph for this pharmaceutical formulation, the dissolution method proposed can be considered suitable for quality control and dissolution profile comparison of different commercial formulations. PMID:26349689

  2. Metronidazole-Induced Bullous Pemphigoid: A Case Report

    PubMed Central

    Moitra, Saibal; Banerjee, Indranil; Sikder, Ayan; Das, Prasanta

    2015-01-01

    Bullous pemphigoid is an autoimmune cutaneous blistering disorder, the exact pathogenesis of which is still not fully elucidated. Drug-induced bullous pemphigoid eruptions are rare but have been reported earlier with the use of frusemide, psoralens, ibuprofen, galantamine hydrobromide, ACE inhibitors like captopril, spironolactone, penicillin, ampicillin, levofloxacin, penicillamine. We hereby report a case of metronidazole induced bullous pemphigoid (BP) in a 52-year-old male patient suffering from liver abscess following 4 days of drug administration. The skin biopsy findings obtained from the patient were consistent with the diagnosis of bullous pemphigoid (BP). Metronidazole was discontinued and symptomatic treatment was offered to the patient. Following withdrawal of metronidazole, the bullae subsided in the next 7-10 days without any significant residual scarring. The causality assessment performed as per the Naranjo algorithm revealed the case to be probable (Naranjo score 7). PMID:26816913

  3. TRICHOMONIASIS—Clinical Trial of Metronidazole (Flagyl®)

    PubMed Central

    Monroe, Stanley E.

    1963-01-01

    Metronidazole was given in various dosage regimens to 97 patients having microscopically diagnosed trichomoniasis. At the first examination after treatment all 97, including 76 to whom metronidazole had been given orally only, were found by culture and wet smear to be free of trichomonads. Reexamination of the 65 patients followed up for periods ranging from two weeks to 14 months revealed reappearance of trichomonads in eight cases. Nineteen husbands were treated. No patient had a recurrence after treatment of the husband. No effect of metronidazole on pregnancy or on fetal development was seen. Side effects, noted in 19 cases (20 per cent), generally were mild and transient and in no case were severe enough to terminate therapy before cure was effected. PMID:13936092

  4. Can bioadhesive nanoparticles allow for more effective particle uptake from the small intestine?

    PubMed

    Reineke, J; Cho, D Y; Dingle, Y L; Cheifetz, P; Laulicht, B; Lavin, D; Furtado, S; Mathiowitz, E

    2013-09-28

    There has been increasing interest in developing bioadhesive nanoparticles due to their great potential as carriers for therapeutics in oral drug delivery systems. Despite decades of research, such a system still has not been successfully implemented. This paper demonstrates the enormous potential of such engineered systems: the incorporation of a bioadhesive coating, poly(butadiene-maleic anhydride-co-L-DOPA) (PBMAD), to non-bioadhesive nanospheres resulted in an enhancement of particle uptake in the small intestine from 5.8±1.9% to 66.9±12.9%. Direct correlation was obtained between bulk tensile strength, in vitro binding to everted intestinal sacs and quantitative in vivo uptake; this data suggests that bulk properties of polymers can be used to predict bioadhesive properties of nano- and microparticles. The differential distribution of the nanospheres to various tissues following uptake suggests surface chemistry plays a significant role in their localization within the body. The results of these studies provide strong support for the use of bioadhesive polymers to enhance nano- and micro-particle uptake from the small intestine for oral drug delivery. PMID:23796432

  5. Fragmentation of Injectable Bioadhesive Hydrogels Affords Chemotherapeutic Macromolecules.

    PubMed

    Yamada, Yuji; Schneider, Joel P

    2016-08-01

    Implantation of drug delivery depots into or proximal to targeted tissue is an effective method to deliver anticancer drugs in a sustained localized manner. Herein, syringe-injectable polydextran aldehyde (PDA)-based bioadhesive gels are prepared that can locally deliver cytotoxins upon their hydrolytic fragmentation. Adhesive gels are formed by mixing doxorubicin (DOX)-functionalized PDA (DOX-PDA) and bovine serum albumin (BSA) using a dual-barrel syringe. Upon mixing and delivery, the DOX-PDA reacts with the cross-linker BSA as well as the extracellular matrix via imine bond formation to define the cohesive and adhesive properties of the gel, respectively. Resulting gels are mechanically rigid (∼10 kPa) and adherent (adhesive stress ∼ 4 kPa). Once formed, the DOX-PDA-BSA gels undergo slow hydrolytic degradation (>2 months) locally releasing free DOX and DOX-PDA as expected. Surprisingly, we found that macromolecules composed of DOX, PDA, and BSA are also released from the bulk material. These DOX-PDA-BSA macromolecules, along with free DOX and DOX-PDA conjugate, are internalized by A549 lung carcinoma cells, resulting in potent cell death. PMID:27388026

  6. Bioadhesion in ascidians: a developmental and functional genomics perspective

    PubMed Central

    Pennati, Roberta; Rothbächer, Ute

    2015-01-01

    The development of bioadhesives inspired from marine animals is a promising approach to generate new tissue-compatible medical components. A number of marine species, through their adhesive properties, also represent significant foulers that become increasingly problematic to aquaculture, shipping or local biodiversity. In order to develop more sophisticated man-made glues and/or efficient fouling resistant surfaces, it is important to understand the mechanical, structural and molecular properties of adhesive organs in selected species. Ascidians are marine invertebrates with larvae that opportunistically attach to almost any type of submerged surface to undergo metamorphosis into permanently sessile adults. Not only do they represent a globally important fouling organism, but they are becoming increasingly popular as model organisms for developmental biology. The latter is due to their phylogenetic position as the sister group to the vertebrates and their cellular and molecular accessibility for experimentation. In this paper, we review the mechanisms of larval adhesion in ascidians and draw conclusions from comparative analyses of selected species. We further discuss how knowledge from a developmental and functional genomics point of view can advance our understanding of cellular and molecular signatures and their hierarchical usage in animal adhesive organs. PMID:25657840

  7. Bioinspired polyethylene terephthalate nanocone arrays with underwater superoleophobicity and anti-bioadhesion properties.

    PubMed

    Liu, Wendong; Liu, Xueyao; Fangteng, Jiaozi; Wang, Shuli; Fang, Liping; Shen, Huaizhong; Xiang, Siyuan; Sun, Hongchen; Yang, Bai

    2014-11-21

    This paper presents a facile method to fabricate bioinspired polyethylene terephthalate (PET) nanocone arrays via colloidal lithography. The aspect ratio (AR) of the nanocones can be finely modulated ranging from 1 to 6 by regulating the etching time. The samples with the AR value of 6 can present underwater superoleophobicity with the underwater oil contact angle (OCA) of 171.8°. The as-prepared PET nanocone arrays perform anti-bioadhesion behavior, which inhibits the formation of the actin cytoskeleton when it used as the substrate for cell culture. Moreover, the oil wettability is temperature controlled after modifying the PET nanocone arrays with PNIPAAm film, and the oil wettability of the functionalized nanocone arrays can be transformed from the superoleophobic state with OCA about 151° to the oleophilic state with OCA about 25° reversibly. Due to the high-throughput, parallel fabrication and cost-efficiency of this method, it will be favourable for researchers to introduce oleophobic properties to various substrate and device surfaces. Due to the superoleophobicity and simple functionalizing properties, the PET nanocone arrays are very promising surfaces for anti-adhesion, self-cleaning and have potential applications in material, medical, and biological fields. PMID:25303770

  8. Gelatin Microgel Incorporated Poly(ethylene glycol)-Based Bioadhesive with Enhanced Adhesive Property and Bioactivity.

    PubMed

    Li, Yuting; Meng, Hao; Liu, Yuan; Narkar, Ameya; Lee, Bruce P

    2016-05-18

    Up to 7.5 wt % of chemically cross-linked gelatin microgel was incorporated into dopamine-modified poly(ethylene glycol) (PEGDM) adhesive to simultaneously improve the material property and bioactivity of the PEG-based bioadhesive. Incorporation of gelatin microgel reduced cure time while it increased the elastic modulus and cross-linking density of the adhesive network. Most notably, the loss modulus values for microgel-containing adhesive were an order of magnitude higher when compared to microgel-free control. This drastic increase in the viscous dissipation ability of the adhesive is attributed to the introduction of reversible physical bonds into the adhesive network with the incorporation of the gelatin microgel. Additionally, incorporation of the microgel increased the adhesive properties of PEGDM by 1.5- to 2-fold. From in vitro cell culture studies, the composite adhesive is noncytotoxic and the incorporation of microgels provided binding site for promoting fibroblast attachment and viability. The subcutaneous implantation study indicated that the microgel-containing PEGDM adhesive is biocompatible and the incorporated microgels provided pockets for rapid cellular infiltration. Gelatin microgel incorporation was demonstrated to be a facile method to simultaneously enhance the adhesive property and the bioactivity of PEG-based adhesive. PMID:27111631

  9. Short-term infection with Helicobacter pylori and 1 week exposure to metronidazole does not enhance gastric mutation frequency in transgenic mice.

    PubMed

    Touati, E; Hofnung, M; Thiberge, J M; Michel, V; Labigne, A; Jenks, P J

    2000-12-01

    The aim of this study was to determine whether exposure of Helicobacter pylori-infected mice to metronidazole resulted in the delivery of mutagenic compounds to the gastric epithelium via the oxygen-insensitive NADPH nitroreductase (RdxA) of H. pylori. C57BL/6 transgenic mice containing the lambda/lacI transgene were inoculated with peptone trypsin broth, H. pylori SS1 or SS1-rdxA(-), an SS1-derived mutant in rdxA. Twelve weeks after inoculation, the mice were treated for 7 days with a control solution or with the mouse equivalent of a human dose of metronidazole 1 g od. Three weeks after completion of treatment, the animals were killed and mutations in the target lacI gene assessed by a transgenic mutagenesis assay system. There was no increase in lacI mutations in cells harvested from mice infected with H. pylori and/or exposed to metronidazole. These data suggest that short-term infection with H. pylori and exposure to metronidazole does not enhance the mutation frequency in the gastric cells of mice. Whether chronic infection and/or repeated exposure to metronidazole or other nitroaromatic compounds causes genetic damage to gastric epithelial cells remains to be determined. PMID:11102419

  10. Bioinspired bioadhesive polymers: dopa-modified poly(acrylic acid) derivatives.

    PubMed

    Laulicht, Bryan; Mancini, Alexis; Geman, Nathanael; Cho, Daniel; Estrellas, Kenneth; Furtado, Stacia; Hopson, Russell; Tripathi, Anubhav; Mathiowitz, Edith

    2012-11-01

    The one-step synthesis and characterization of novel bioinspired bioadhesive polymers that contain Dopa, implicated in the extremely adhesive byssal fibers of certain gastropods, is reported. The novel polymers consist of combinations of either of two polyanhydride backbones and one of three amino acids, phenylalanine, tyrosine, or Dopa, grafted as side chains. Dopa-grafted hydrophobic backbone polymers exhibit as much as 2.5 × the fracture strength and 2.8 × the tensile work of bioadhesion of a commercially available poly(acrylic acid) derivative as tested on live, excised, rat intestinal tissue. PMID:23008096

  11. Effects of Azithromycin, Metronidazole, Amoxicillin, and Metronidazole plus Amoxicillin on an In Vitro Polymicrobial Subgingival Biofilm Model

    PubMed Central

    Teles, Flavia; Starr, Jacqueline R.; Feres, Magda; Patel, Michele; Martin, Lynn

    2015-01-01

    Chronic periodontitis is one of the most prevalent human diseases and is caused by dysbiosis of the subgingival microbiota. Treatment involves primarily mechanical disruption of subgingival biofilms and, in certain cases, adjunctive use of systemic antibiotic therapy. In vitro biofilm models have been developed to study antimicrobial agents targeting subgingival species. However, these models accommodate a limited number of taxa, lack reproducibility, and have low throughput. We aimed to develop an in vitro multispecies biofilm model that mimics subgingival plaque, to test antimicrobial agents. Biofilms were cultivated using the Calgary Biofilm Device and were exposed to amoxicillin (AMX), metronidazole (MTZ), azithromycin (AZM), and AMX-MTZ at four different concentrations for 12, 24, or 36 h. Chlorhexidine (CHX) (0.12%) was used as the positive control. The compositions of the biofilms were analyzed by checkerboard DNA-DNA hybridization, and the percent reduction in biofilm metabolic activity was determined using 2,3,5-triphenyltetrazolium chloride and spectrophotometry. Thirty-five of the 40 species used in the inoculum were consistently recovered from the resulting in vitro biofilms. After 36 h of exposure at the 1:27 dilution, AMX-MTZ reduced metabolic activity 11% less than CHX (q = 0.0207) but 54% more than AMX (q = 0.0031), 72% more than MTZ (q = 0.0031), and 67% more than AZM (q = 0.0008). Preliminary evidence of a synergistic interaction between AMX and MTZ was also observed. In summary, we developed reproducible biofilms with 35 subgingival bacterial species, and our results suggested that the combination of AMX and MTZ had greater antimicrobial effects on these in vitro multispecies biofilms than expected on the basis of the independent effects of the drugs. PMID:25733510

  12. Anti-Bioadhesive Coating Based on Easy to Make Pseudozwitterionic RAFT Block Copolymers for Blood-Contacting Applications.

    PubMed

    Nehache, Sabrina; Yeh, Chin-Cheng; Semsarilar, Mona; Deratani, André; Chang, Yung; Quemener, Damien

    2016-01-01

    Amphiphilic diblock copolymer containing randomly distributed positive and negative charged monomers are synthesized using RAFT polymerization technique to be used as anti-bioadhesion coatings for hydrophobic surfaces. Quaternized 2-(dimethylamino) ethyl methacrylate and potassium 3-sulfopropyl methacrylate (P[qDMAEMA-co-KSPMA]) are randomly polymerized to yield an anti-bioadhesion block which is, in one pot, copolymerized with styrene as an anchoring block. This copolymer has demonstrated high anti-bioadhesion properties to avoid the blood clotting in medical devices through a simple and facile approach to preparation of pseudozwitterionic copolymers. PMID:26222768

  13. Gastroretentive Ranitidine Hydrochloride Tablets with Combined Floating and Bioadhesive Properties: Factorial Design Analysis, In Vitro Evaluation and In Vivo Abdominal X-Ray Imaging.

    PubMed

    Abduljabbar, Hana N; Badr-Eldin, Shaimaa M; Aldawsari, Hibah M

    2015-01-01

    Ranitidine HCl is an H2-antagonist that suffers from low oral bioavailability of 50%. The site-specific absorption from the upper part of the small intestine and the colonic metabolism of the drug could partially contribute to its reduced bioavailability. To surmount these drawbacks, this work aimed at the formulation of Ranitidine HCl gastroretentive floating-biaodhesive tablets. A 3(2) factorial design was applied to assess the effects of matrix former (HPMC K100M): drug ratio, and the release retardant (Carbopol 971) amount on the characteristics of the tablets prepared using direct compression technique. The prepared tablets were thoroughly evaluated for physical properties, floating, swelling, bioadhesive and in vitro release behaviors. Statistical analysis of the results revealed significant effects for both formulation variables on the swelling index, maximum detachment force and cumulative percent drug released after 6 hours. In addition, the matrix- former: drug ratio showed a statistically significant effect on the floating lag time. Kinetic analysis of the release data indicated Higuchi diffusion kinetics and anomalous transport mechanism for all formulations. Scanning electron micrographs of the selected tablet formulation; F8, revealed intact surface without any perforations or channels in the dry state, while polymer expansion (relaxation) with some perforated areas were observed on the surface of the tablets after 12 hours dissolution in 0.1 N HCl. Furthermore, in vivo abdominal x-ray imaging showed good floating behavior of the selected formulation; F8, for up to 6 hours with appropriate bioadhesive property. In conclusion, the selected ranitidine HCl floating-bioadhesive tablets could be regarded as a promising gastroretentive drug delivery system that could deliver the drug at a controlled rate. PMID:26051347

  14. Potentials of chitosan-based delivery systems in wound therapy: bioadhesion study.

    PubMed

    Hurler, Julia; Skalko-Basnet, Nataša

    2012-01-01

    Chitosan is currently proposed to be one of the most promising polymers in wound dressing development. Our research focuses on its potential as a vehicle for nano-delivery systems destined for burn therapy. One of the most important features of wound dressing is its bioadhesion to the wounded site. We compared the bioadhesive properties of chitosan with those of Carbopol, a synthetic origin polymer. Chitosan-based hydrogels of different molecular weights were first analyzed by texture analysis for gel cohesiveness, adhesiveness and hardness. In vitro release studies showed no difference in release of model antimicrobial drug from the different hydrogel formulations. Bioadhesion tests were performed on pig ear skin and the detachment force, necessary to remove the die from the skin, and the amount of remaining formulation on the skin were determined. Although no significant difference regarding detachment force could be seen between Carbopol-based and chitosan-based formulations, almost double the amount of chitosan formulation remained on the skin as compared to Carbopol formulations. The findings confirmed the great potential of chitosan-based delivery systems in advanced wound therapy. Moreover, results suggest that formulation retention on the ex vivo skin samples could provide deeper insight on formulation bioadhesiveness than the determination of detachment force. PMID:24956514

  15. A novel ketoconazole bioadhesive effervescent tablet for vaginal delivery: design, in vitro and 'in vivo' evaluation.

    PubMed

    Wang, Lei; Tang, Xing

    2008-02-28

    Bioadhesive tablet formulations of ketoconazole for vaginal delivery were studied. Carbomer (Carbopol 974P, Carbopol 934P), hydroxypropylmethyl cellulose (HPMC) and hydroxypropyl cellulose (HPC) were used as candidate bioadhesive polymers. Effervescent was incorporated into the formulations as a disintegration agent. The swelling behavior and bioadhesive strength of the drug-free tablets were investigated. Carbopol 934P was selected as biopolymer in combination with HPMC or HPC at different ratios to develop five drug-loaded formulations. The swellings, tackiness and in vitro release were studied on the tablets. A good sustained effect and a moderate bioadhesion were obtained with the tablets. The formulation containing 100mg of effervescent, with the Carbopol 934P:HPC ratio of 1:9, seemed to be the optimum one for the tablet. In vivo drug residence tests were carried out by administering the preferred formulation to female rats. The results showed that the drug remaining followed a one-order model. Even after 24h of administration in vagina of rats, 17% of the original employed drug was retained on the vaginal tissue. Our study may provide a potential vaginal tablet formulation of ketoconazole against Candida albicans. PMID:17920795

  16. Spray-dried Amioca starch/Carbopol 974P mixtures as buccal bioadhesive carriers.

    PubMed

    Ameye, D; Mus, D; Foreman, P; Remon, J P

    2005-09-14

    In the present study, spray-dried Amioca starch/Carbopol 974P mixtures were evaluated as potential buccal bioadhesive tablets. Carbopol (C 974P) concentrations from 5 to 75% were tested. All spray-dried mixtures showed a comparable or better bioadhesive capacity compared to a reference formulation (DDWM/C 974P 95/5). The bioadhesive capacities of Amioca/Carbopol 974P mixtures were improved by spray-drying. All spray-dried mixtures showed significantly higher work of adhesion values compared to their equivalent physical mixtures. The influence of Carbopol concentration on the in vivo adhesion time of placebo tablets and in vitro miconazole nitrate release was tested. The ratio Amioca/C 974P 70/30 showed the longest in vivo adhesion time (24.5+/-8.5 h). Lower and higher C 974P concentrations had a shorter in vivo adhesion time. The mixtures containing between 15 and 30% C 974P could all sustain the in vitro miconazole nitrate release over 20 h. Again, lower and higher C 974P concentrations showed a faster in vitro miconazole release. The drug loading capacity of a spray-dried mixture containing 20% C 974P was investigated in vivo in dogs using testosterone as model drug. The spray-dried mixture could be loaded with 60% drug without loosing its in vivo bioadhesive and pharmacokinetic properties. PMID:16019172

  17. New approach for local delivery of rapamycin by bioadhesive PLGA-carbopol nanoparticles.

    PubMed

    Zou, Weiwei; Cao, Guangqing; Xi, Yanwei; Zhang, Na

    2009-01-01

    Local delivery of antiproliferative drugs encapsulated in biodegradable nanoparticles has shown promise as an experimental strategy for preventing vascular restenosis development. The general aim of this work was to develop polymeric nanoparticle carriers with bioadhesive properties, and to evaluate its adjuvant potential for local, intramural delivery of rapamycin for inhibition of restenosis. The bioadhesive rapamycin-loaded PLGA nanoparticles were obtained by applying carbopol 940 of different concentrations as stabilizer and bioadhesive agent. The resultant nanoparticles were characterized concerning physicochemical properties such as morphology, particle size, zeta potential, entrapment efficiency, drug loading, drug release in vitro, stability in vitro as well as the arterial uptake and retention ability in an ex-vivo model. The results revealed that carbopol could serve as a better stabilizer in the preparation of rapamycin-loaded PLGA nanoparticles compared with PVA, and the physicochemical characteristics of the obtained PLGA nanoparticles were affected by the concentration of carbopol. Furthermore, it was found that carbopol could impart the nanoparticles with bioadhesive properties, improving the rentention and uptake of nanoparticles in the arterial wall, benefiting the nanoparticles for efficient localization of therapeutic agents in restenosis site. Cell viability assay results showed that blank PLGA-carbopol nanoparticles exhibited low toxicity and excellent biocompatibility and rapamycin-loaded nanoparticles with a smaller particle size (< 200 nm) had an increased antiproliferative effect on cells in comparison to free drug. These results indicated that this research might provide a potential experimental basis for the further study of carbopol stabilized bioadhesive nanoparticles against restenosis in vivo. PMID:19555304

  18. Per-oral extended-release bioadhesive tablet formulation of verapamil HCl.

    PubMed

    Elkheshen, Seham; Yassin, Alaa Eldeen B; Alkhaled, Fayza

    2003-06-01

    The objective of this study was to formulate a hydrogel-forming bioadhesive drug delivery system for oral administration of verapamil HCl (VP). This system is a non-distintegrating gastro-retentive tablet to allow continuous slow release of VP in the stomach medium where it is more soluble. Different formulate of VP tablets were prepared by compression using various proportions of hydroxypropyl cellulose (HPC) and carbopol 934p (CP). The effect of polymer concentration on the release profile, water uptake and in vitro bioadhesion was studied. Five formulae (F3-F7) exhibited slow release profiles. Formulations F6 (40% HPC and 30% CP) and F7 (40% HPC and 40% CP) had the slowest. They showed 63.6 and 52.2% drug release, respectively, after 12 hours. The kinetic analysis of the release data demonstrated that the bigbest linearity were achieved when data fitted in Higuchi equation rather than zero or first order equations. They had n values close to 0.5 that confirming their Higuchi diffusion. F3 showed the highest swelling index (101.2%), however, the detachment force was intermediate (1.427 N/cm2). Formulae (F4-F7) showed relatively strong in-vitro bioadhesive force. They had detachment forces higher than 1 N/cm2. In general, a delay in drug release and an increase in the in-vitro bioadhesion was seen with the increase in both polymer concentrations. The in vitro data revealed that Formulae F4-F7 served the dual purpose of bioadhesion and sustained release. PMID:14526657

  19. Efficacy of the treatment of dogs with leishmaniosis with a combination of metronidazole and spiramycin.

    PubMed

    Pennisi, M G; De Majo, M; Masucci, M; Britti, D; Vitale, F; Del Maso, R

    2005-03-12

    Twenty-seven dogs infected naturally with Leishmania infantum were used in a randomised controlled trial to compare the clinical and parasitological efficacy of an oral treatment with a combination of metronidazole and spiramycin (13 dogs) with the efficacy of conventional treatment with meglumine antimonate and allopurinol (14 dogs) as controls. In the test group one dog had to be withdrawn from the treatment because it developed pemphigus foliaceus; 10 of the dogs were clinically responsive but none was cured parasitologically. In the control group four dogs were withdrawn from the treatment because of side effects; eight of the dogs were clinically responsive but none was cured parasitologically. The control group showed signs of improvement after an average of 30 days, whereas the test group did not show signs of improvement until after an average of 45 days. PMID:15789648

  20. Bioinspired polyethylene terephthalate nanocone arrays with underwater superoleophobicity and anti-bioadhesion properties

    NASA Astrophysics Data System (ADS)

    Liu, Wendong; Liu, Xueyao; Fangteng, Jiaozi; Wang, Shuli; Fang, Liping; Shen, Huaizhong; Xiang, Siyuan; Sun, Hongchen; Yang, Bai

    2014-10-01

    This paper presents a facile method to fabricate bioinspired polyethylene terephthalate (PET) nanocone arrays via colloidal lithography. The aspect ratio (AR) of the nanocones can be finely modulated ranging from 1 to 6 by regulating the etching time. The samples with the AR value of 6 can present underwater superoleophobicity with the underwater oil contact angle (OCA) of 171.8°. The as-prepared PET nanocone arrays perform anti-bioadhesion behavior, which inhibits the formation of the actin cytoskeleton when it used as the substrate for cell culture. Moreover, the oil wettability is temperature controlled after modifying the PET nanocone arrays with PNIPAAm film, and the oil wettability of the functionalized nanocone arrays can be transformed from the superoleophobic state with OCA about 151° to the oleophilic state with OCA about 25° reversibly. Due to the high-throughput, parallel fabrication and cost-efficiency of this method, it will be favourable for researchers to introduce oleophobic properties to various substrate and device surfaces. Due to the superoleophobicity and simple functionalizing properties, the PET nanocone arrays are very promising surfaces for anti-adhesion, self-cleaning and have potential applications in material, medical, and biological fields.This paper presents a facile method to fabricate bioinspired polyethylene terephthalate (PET) nanocone arrays via colloidal lithography. The aspect ratio (AR) of the nanocones can be finely modulated ranging from 1 to 6 by regulating the etching time. The samples with the AR value of 6 can present underwater superoleophobicity with the underwater oil contact angle (OCA) of 171.8°. The as-prepared PET nanocone arrays perform anti-bioadhesion behavior, which inhibits the formation of the actin cytoskeleton when it used as the substrate for cell culture. Moreover, the oil wettability is temperature controlled after modifying the PET nanocone arrays with PNIPAAm film, and the oil wettability of the

  1. Electrospraying technique for the fabrication of metronidazole contained PLGA particles and their release profile.

    PubMed

    Prabhakaran, Molamma P; Zamani, Maedeh; Felice, Betiana; Ramakrishna, Seeram

    2015-11-01

    Advanced engineering of materials for the development of drug delivery devices provides scope for novel and versatile strategies for treatment of various diseases. 'Electrospraying' was used to prepare PLGA microparticles and further encapsulate the drug, metronidazole (Met) within the particles to function as a drug delivery system. Two different solvents were utilized for the preparation of drug loaded PLGA particles, whereby the polymeric solution in dichloromethane (DCM) produced particles of bigger sizes than using trifluoroethanol (TFE). Scanning electron microscopy showed the spherical morphology of the particles, with sizes of 3946±407nm and 1774±167nm, respectively for PLGA-Met(DCM) and PLGA-Met(TFE). The FTIR spectroscopy proved the incorporation of metronidazole in the polymer, but without any specific drug-polymer interaction. The release of the drug from the particles was studied in phosphate buffered saline, where a sustained drug release was obtained for at least 41days. Cytotoxicity evaluation of the drug extract using mesenchymal stem cells (MSCs) showed not hindering the proliferation of MSCs, and the cell phenotype was retained after incubation in the drug containing media. Electrospraying is suggested as a cost-effective and single step process for the preparation of polymeric microparticles for prolonged and controlled release of drug. PMID:26249566

  2. Once Daily Dosing of Ceftriaxone and Metronidazole in Children With Perforated Appendicitis

    PubMed Central

    Ally, Saudia; Kelly, Brian; Kays, David; Thames, Lisa

    2016-01-01

    OBJECTIVES: The aim of this study was to compare hospital length of stay and rate of infectious complications in children with perforated appendicitis based on the postoperative antibiotic administered. METHODS: This study was a retrospective analysis of children with perforated appendicitis who underwent an appendectomy at a large academic medical center from 2008 to 2013. The primary outcome was hospital length of stay. The secondary outcomes were rates of abscess formation, wound infection, and 30-day readmissions. RESULTS: One hundred and twenty-three patients were included. Sixty-six patients (53%) were administered ceftriaxone and metronidazole once daily; 57 (47%) were administered other antibiotic regimens, which consisted of single, double, or triple antibiotic therapy with a beta-lactam backbone. There was no difference between the groups in terms of postoperative length of stay (5.7 versus 5.8 days, p = 0.83), postoperative abscess rate (8% versus 4%, p = 0.57), postoperative wound infection rate (5% versus 2%, p = 0.73), and 30-day readmissions (3% versus 11%, p = 0.19). CONCLUSIONS: While there was no statistically significant difierence in the outcomes evaluated, the rate of infectious complications was twofold higher in those given ceftriaxone and metronidazole than in others. A larger prospective randomized controlled trial is warranted to better understand the risks of using these agents. PMID:27199621

  3. Development and In Vivo Evaluation of a Novel Histatin-5 Bioadhesive Hydrogel Formulation against Oral Candidiasis

    PubMed Central

    Kong, Eric F.; Tsui, Christina; Boyce, Heather; Ibrahim, Ahmed; Hoag, Stephen W.; Karlsson, Amy J.; Meiller, Timothy F.

    2015-01-01

    Oral candidiasis (OC), caused by the fungal pathogen Candida 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 evaluated in vitro for gel viscosity, Hst-5 release rate from the gel, and killing potency and, more importantly, was tested in vivo in our mouse model of OC. The findings demonstrated a controlled sustained release of Hst-5 from the polymer and rapid killing ability. Based on viable C. albicans counts recovered from tongues of treated and untreated mice, three daily applications of the formulation beginning 1 day postinfection with C. albicans were 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. PMID:26596951

  4. In vitro effect of tinidazole and furazolidone on metronidazole-resistant Trichomonas vaginalis.

    PubMed Central

    Narcisi, E M; Secor, W E

    1996-01-01

    Trichomonas vaginalis is a common sexually transmitted protozoan parasite. Although often considered simply a nuisance infection, T. vaginalis has been implicated in premature rupture of placental membranes and increases in the risk of acquiring human immunodeficiency virus. Metronidazole, a 5-nitroimidazole, is currently the drug of choice to treat T. vaginalis infection. Because some patients have severe reactions to metronidazole and others are infected with metronidazole-resistant T. vaginalis, we were prompted to investigate alternative therapies. Tinidazole, another 5-nitroimidazole used in other countries to treat T. vaginalis infections, and furazolidone, a nitrofuran presently used to treat giardiasis and infections with some anaerobic enteric bacteria, were investigated for effectiveness against 9 metronidazole-susceptible and 12 metronidazole-resistant T. vaginalis patient isolates. The in vitro aerobic and anaerobic minimum lethal concentrations (MLC) and the time for drug efficacy were determined. Tinidazole killed the metronidazole-susceptible isolates at a low MLC but was effective against only 4 of the 12 metronidazole-resistant isolates. In contrast, furazolidone was effective at a low MLC for all isolates. When tinidazole was effective, it required > 6 h to kill trichomonads. However, furazolidone killed both metronidazole-susceptible and resistant trichomonads within 2 to 3 h of exposure. These data suggest that furazolidone may be a good candidate for treating metronidazole-resistant trichomoniasis and that further investigation of this drug is warranted. PMID:8723451

  5. Natural antimicrobials subtilosin and lauramide arginine ethyl ester synergize with conventional antibiotics clindamycin and metronidazole against biofilms of Gardnerella vaginalis but not against biofilms of healthy vaginal lactobacilli.

    PubMed

    Algburi, Ammar; Volski, Anna; Chikindas, Michael L

    2015-07-01

    The purpose of this study was to evaluate the ability of clindamycin and metronidazole to synergize with natural antimicrobials against biofilms of bacterial vaginosis (BV)-associated Gardnerella vaginalis. Minimum bactericidal concentrations for biofilm cells (MBCs-B) were determined for each antimicrobial. The MBCs-B of lauramide arginine ethyl ester (LAE), subtilosin, clindamycin and metronidazole were 50, 69.5, 20 and 500 μg mL(-1), respectively. A checkerboard assay and isobologram were used to analyze the type of interactions between these antimicrobials. The combination of metronidazole with natural antimicrobials did not inhibit planktonic lactobacilli. Clindamycin with either LAE or with subtilosin was inhibitory for planktonic but not for biofilm-associated lactobacilli. All tested antimicrobial combinations were inhibitory for BV-associated Mobiluncus curtisii and Peptostreptococcus anaerobius. LAE and subtilosin synergized with clindamycin and metronidazole against biofilms of G. vaginalis but not biofilm-associated vaginal lactobacilli. The biofilms of BV-associated pathogens can be controlled by synergistically acting combinations of conventional antibiotics and natural antimicrobials which will help better management of current antibiotics, especially considering robust bacterial resistance. Our findings create a foundation for a new strategy in the effective control of vaginal infections. PMID:25838136

  6. THE EFFICACY OF THREE MEDICINAL PLANTS; GARLIC, GINGER AND MIRAZID AND A CHEMICAL DRUG METRONIDAZOLE AGAINST CRYPTOSPORIDIUM PARVUM: II-HISTOLOGICAL CHANGES.

    PubMed

    Abouel-Nour, Mohamed F; El-Shewehy, Dina Magdy M; Hamada, Shadia F; Morsy, Tosson A

    2016-04-01

    Cryptosporidiosis parvum is a zoonotic protozoan parasite infects intestinal epithelial cells of man and animals causing a major health problem. This study was oriented to evaluate the protective and curative capacity of garlic, ginger and mirazid in comparison with metronidazole drug (commercially known) against Cryptosporidium in experimental mice. Male Swiss Albino mice experimentally infected with C. parvum were treated with medicinal plants extracts (Ginger, Mirazid, and Garlic) as compared to chemical drug Metronidazole. Importantly, C. parvum-infected mice treated with ginger, Mirazid, garlic and metronidazole showed a complete elimination in shedding oocysts by 9th day PI. The reduction and elimination of shedding oocysts in response to the treatments might be attributable to a direct effect on parasite growth in intestines, sexual phases production and/or the formation of oocysts. The results were evaluated histopathological examination of ideum section of control mice (uninfected, untreated) displayed normal architecture of the villi. Examiination of infected mice ileum section (infected, untreated) displayed histopathological alterations from uninfected groups. Examination of ileum section prepared from mice treated with garlic, ginger, mirazid, and metronidazole displayed histopathological alterations from that of the control groups, and showed marked histologic correction in the pattern with the four regimes used in comparison to control mice. Garlic successfully eradicated oocysts of infected mice from stool and intestine. Supplementation of ginger to infected mice markedly corrected elevation in the inflammatory risk factors and implied its potential antioxidant, anti-inflammatory and immunomodulatory capabilities. Infected mice treated with ginger, mirazid, garlic and metronidazole showed significant symptomatic improvements during treatment. PMID:27363055

  7. Ex vivo bioadhesion and in vivo testosterone bioavailability study of different bioadhesive formulations based on starch-g-poly(acrylic acid) copolymers and starch/poly(acrylic acid) mixtures.

    PubMed

    Ameye, D; Voorspoels, J; Foreman, P; Tsai, J; Richardson, P; Geresh, S; Remon, J P

    2002-02-19

    Starch-g-poly(acrylic acid) copolymers or grafted starches synthesized by 60Co irradiation or chemical modification and co-freeze-dried starch/poly(acrylic acid) mixtures were evaluated on their ex vivo bioadhesion capacity. The buccal absorption of testosterone from a bioadhesive tablet formulated with the grafted starches or starch/poly(acrylic acid) mixtures was investigated. The results were compared to a reference formulation (physical mixture of 5% Carbopol 974P and 95% Drum Dried Waxy Maize). Rice starch-based irradiated grafted starches showed the best bioadhesion results. Partial neutralization of the acrylic acid with Ca(2+) ions resulted in significantly higher bioadhesion values compared to the reference. Ca(2+) and Mg(2+) partially neutralized maltodextrin-based irradiated grafted starches showed significantly higher bioadhesion values compared to the reference formulation. The chemically modified grafted starches showed significantly higher adhesion force values than for the reference tablet. None of the co-freeze-dried starch/poly(acrylic acid) mixtures showed significantly higher bioadhesion results than the reference (Bonferroni test, P<0.05). A chemically modified grafted starch could sustain the 3 ng/ml plasma testosterone target concentration during +/- 8 h (T(>3 ng/ml)). By lyophilization of a partially neutralized irradiated grafted starch, the in vivo adhesion time (22.0 +/- 7.2 h) and the T(>3 ng/ml) (13.5 +/- 1.3 h) could be increased. The absolute bioavailability of the lyophilized formulation approached the reference formulation. Some of the grafted starches showed to be promising buccal bioadhesive drug carriers for systemic delivery. PMID:11853929

  8. Multidisciplinary Analysis of a Nontoxigenic Clostridium difficile Strain with Stable Resistance to Metronidazole

    PubMed Central

    Moura, Ines; Monot, Marc; Tani, Chiara; Barbanti, Fabrizio; Norais, Nathalie; Dupuy, Bruno; Bouza, Emilio; Mastrantonio, Paola

    2014-01-01

    Stable resistance to metronidazole in a nontoxigenic Clostridium difficile strain was investigated at both the genomic and proteomic levels. Alterations in the metabolic pathway involving the pyruvate-ferredoxin oxidoreductase were found, suggesting that reduction of metronidazole, required for its activity, may be less efficient in this strain. Proteomic studies also showed a cellular response to oxidative stress. PMID:24913157

  9. Multidisciplinary analysis of a nontoxigenic Clostridium difficile strain with stable resistance to metronidazole.

    PubMed

    Moura, Ines; Monot, Marc; Tani, Chiara; Spigaglia, Patrizia; Barbanti, Fabrizio; Norais, Nathalie; Dupuy, Bruno; Bouza, Emilio; Mastrantonio, Paola

    2014-08-01

    Stable resistance to metronidazole in a nontoxigenic Clostridium difficile strain was investigated at both the genomic and proteomic levels. Alterations in the metabolic pathway involving the pyruvate-ferredoxin oxidoreductase were found, suggesting that reduction of metronidazole, required for its activity, may be less efficient in this strain. Proteomic studies also showed a cellular response to oxidative stress. PMID:24913157

  10. Novel sustained release, swellable and bioadhesive gastroretentive drug delivery system for ofloxacin.

    PubMed

    Chavanpatil, Mahesh D; Jain, Paras; Chaudhari, Sachin; Shear, Rajesh; Vavia, Pradeep R

    2006-06-19

    Oral sustained release gastroretentive dosage forms offer many advantages for drugs having absorption from upper gastrointestinal tract and improve the bioavailability of medications that are characterized by a narrow absorption window. A new gastroretentive sustained release delivery system was developed with floating, swellable and bioadhesive properties. All these properties were optimized and evaluated. Various release retarding polymers like psyllium husk, HPMC K100M and a swelling agent, crosspovidone in combinations were tried and optimized to get the release profile for 24 h. Formulations were evaluated for in vitro drug release profile, swelling characteristics and in vitro bioadhesion property. The in vitro drug release followed Higuchi kinetics and the drug release mechanism was found to be of anomalous or non-Fickian type. For the developed formulation, the value of n was found to be 0.5766 while for the marketed formulation the value was 0.5718 indicating the anomalous transport. The high water uptake leading to higher swelling of the tablet supported the anomalous release mechanism of ofloxacin. The similarity factor f2 was found to be 91.12 for the developed formulation indicating the release was similar to that of the marketed formulation (Zanocin OD). The swelling properties were increased with increasing crosspovidone concentration and contributed significantly in drug release from the tablet matrix. The bioadhesive property of the developed formulation was found to be significant (P < 0.005) in combination as compared to HPMC K100M and psyllium husk alone. PMID:16567072

  11. Peptide derived from Pvfp-1 as bioadhesive on bio-inert surface.

    PubMed

    Jiang, Zhen; Yu, Yabiao; Du, Lina; Ding, Xiyu; Xu, Hui; Sun, Yanan; Zhang, Qiqing

    2012-02-01

    Surface property is one important characteristic of materials, especially for ones that are bio-inert but designed for bio-medical application. In this study, we designed a series of peptides and compared their capacities as bioadhesive to improve the surface bioactivity of bio-inert material. The peptides were designed according to the sequence of Perna viridis foot protein 1 (Pvfp-1), one of the Mfp-1s (mussel foot protein 1) which play key roles in wet adhesion of mussel byssus. And the Teflon (PTFE) was chosen as a model of bio-inert material. With adsorption, adhesion and coating analysis, it was found that peptide C2 (M) (derived from the non-repeating region of Pvfp-1, contains modified DOPA) has superior coating and adhesion abilities especially on the bio-inert surface of PTFE. After coating with peptide C2 (M), the cell adhesion and spreading of osteoblast MC3T3-E1 cells on PTFE were significantly improved compared with those on non-coated surface, and the peptide-coating did not show any cell toxicity. Therefore, peptide C2 (M) is effective for improving the bioactivity of bio-inert PTFE, and could be potentially used as a bioadhesive on other bio-inert materials for biomedical application. Moreover, this study also provided new insights in designing other peptide-based bioadhesive materials. PMID:22079698

  12. Temperature Stability and Bioadhesive Properties of Δ9-Tetrahydrocannabinol Incorporated Hydroxypropylcellulose Polymer Matrix Systems

    PubMed Central

    Repka, Michael A.; Munjal, Manish; ElSohly, Mahmoud A.; Ross, Samir A.

    2010-01-01

    The purpose of this study was to determine and compare the bioadhesive profiles of hydroxypropylcellulose (HPC) polymer matrices as a function of Δ9-tetrahydrocannabinol (THC) content. In addition, the effect of processing temperature on the stability of THC and its extent of degradation to cannabinol (CBN) was investigated. A hot-melt cast molding method was used to prepare HPC polymer matrix systems incorporated with THC at 0, 4, 8, and 16 percent. Bioadhesive measurements including peak adhesive force, area under the curve, and elongation at adhesive failure were recorded utilizing the TA.XT2i Texture Analyzer™. Data obtained from these tests at various contact time intervals suggested that the incorporation of THC led to an increase in the bioadhesive strength of the HPC polymer matrices. To determine the stability of THC and the resulting CBN content in the matrices, three different processing temperatures were utilized (120, 160, and 200°C). Post-production High Performance Liquid Chromotography (HPLC) analysis revealed that the processed systems contained at least 94% of THC and the relative percent formation of CBN was 0.5% at 120°C and 0.4% at 160°C compared to 1.6% at 200°C. These findings indicate that the cannabinoid may be a plausible candidate for incorporation into systems utilizing hot-melt extrusion techniques for the development of an effective mucoadhesive transmucosal matrix system for delivery of THC. PMID:16455601

  13. Formulation and evaluation of sustained release bioadhesive tablets of ofloxacin using 32 factorial design

    PubMed Central

    Gangurde, Hemant H; Chordiya, Mayur A; Tamizharasi, S; Senthilkumaran, K; Sivakumar, T

    2011-01-01

    Background: Oral sustained release gastroretentive dosage forms offer many advantages for drugs having absorption from upper gastrointestinal tract and improve the bioavailability of medications that are characterized by narrow absorption window. The aim of current study was to design sustained release bioadhesive gastroretentive dosage form of ofloxacin. Materials and Methods: A 32 full factorial design was employed to systematically study the drug release profile and bioadhesive strength. Carbopol 934P and HPMC K100M were selected as the independent variables. Compatibility between drug and polymer was tested by fourier transform infrared (FTIR) and X-ray diffraction (XRD) techniques. Tablets were prepared by direct compression and were evaluated for tablet characteristics, swelling study, adhesion strength, percent drug released, radiographic imaging study and stability study. The optimized formulation was then compared with marketed formulation (Oflin OD®). Results: Tablets prepared showed good tablet characteristics, optimum swelling property, and good adhesion strength with high detachment force. Most of the formulations including the optimized formulation followed Higuchi kinetics and the drug release mechanism was found to be anomalous. Radiographic image proved that tablet remains intact in its structural integrity and shape in stomach up to 24 h. The short-term accelerated stability testing was carried out for the optimized formulation, and results revealed that drug content, in-vitro dissolution and all other parameters were within acceptable limits. Conclusion: Thus, the prepared bioadhesive gastroretentive ofloxacin tablet may prove to be a potential candidate which increases the bioavailability of ofloxacin for any intragastric condition. PMID:23071937

  14. Tribulus terrestris ameliorates metronidazole-induced spermatogenic inhibition and testicular oxidative stress in the laboratory mouse

    PubMed Central

    Kumari, Mrinalini; Singh, Poonam

    2015-01-01

    Objective: The present study was undertaken to evaluate the protective effects of the fruit extract of Tribulus terrestris (TT) on the metronidazole (MTZ)-induced alterations in spermatogenesis, sperm count, testicular functions, and oxidative stress. Materials and Methods: Thirty adult Swiss strain mice were divided into six groups. Animals of Groups I and II served as untreated and vehicle-treated controls, while that of Groups III and IV were administered with MTZ (500 mg/kg BW/day) and TT (200 mg/kg BW/day) alone for 28 days, respectively. Low (100 mg/kg BW/day) and high (200 mg/kg BW/day) doses of TT along with MTZ (500 mg/kg BW/day) were administered for 28 days in the mice of Groups V and VI, respectively. Twenty four hours after the last treatment, all the animals were euthanized to study the histological changes in the testis and sperm count in the epididymis. Testicular functional markers, lipid peroxidation (LPO) and the activities of antioxidant enzymes, e.g., superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, were also assessed in the mice of all the groups. Results: Metronidazole caused marked alterations in the testicular weight, spermatogenesis, activities of antioxidant enzymes, lactate dehydrogenase, alkaline phosphatase, and the level of LPO. The epididymal sperm count also declined significantly in MTZ-treated group. These changes were partially restored following co-administration of 500 mg/kg BW/day of MTZ and 100 mg/kg BW/day of TT. However, in the mice co-administered with 500 mg/kg BW/day of MTZ and 200 mg/kg BW/day of TT, the changes reverted back completely, similar to that of the controls. Conclusion: The fruit extract of TT ameliorates the MTZ-induced alterations in the testis. PMID:26069369

  15. Formulation and evaluation of different floating tablets containing metronidazole to target stomach.

    PubMed

    Loh, Zhiao C; Elkordy, Amal A

    2015-01-01

    The purpose of this study is to formulate and develop tablets dosage form containing Metronidazole which has swelling and floating properties as a gastroretentive controlled-release drug delivery system to improve drug bioavailability. Fifteen different formulations of effervescence-forming floating systems were designed using HPMC K15M, xanthan gum, co-povidone, Eudragit® RL PO, pluronic® F-127 and/or polypropylene foam powder as swelling agents and sodium bicarbonate with/ without citric acid as gas-forming agents at different compositions. Six out of these 15 formulations which have satisfactory tablet floating behaviour were further studied with the incorporation of Metronidazole. The tablets were evaluated based on tablet physicochemical properties, floating behaviour, swelling ability and drug dissolution studies which were carried out using 0.1M HCl at 37°C for 8 hours. Furthermore, evaluation of the powder mixtures using Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) and scanning electron microscope (SEM) were investigated. Most of the tablets show good physicochemical properties except for F11 which contains pluronic® F-127 as its release-retarding matrix-forming polymer. Other formulations show high swelling capacity, ability to float for at least 8 hours in vitro and have sustained drug release characteristics. Data obtained indicated that F3 which contains HPMC (12.5%w/w), xanthan gum (25%w/w), co-povidone (12.5%w/w) and sodium bicarbonate (31.7%w/w) is a suitable formulation with short floating lag time, good floating behaviour and sustained drug release for at least 8 hours in vitro with a zero order kinetic. Combinations of HPMC K15M and xanthan gum as swelling agents show synergistic effect in retarding drug release and are suitable in providing the most sustained drug release system. PMID:25924732

  16. Zero order and signal processing spectrophotometric techniques applied for resolving interference of metronidazole with ciprofloxacin in their pharmaceutical dosage form

    NASA Astrophysics Data System (ADS)

    Attia, Khalid A. M.; Nassar, Mohammed W. I.; El-Zeiny, Mohamed B.; Serag, Ahmed

    2016-02-01

    Four rapid, simple, accurate and precise spectrophotometric methods were used for the determination of ciprofloxacin in the presence of metronidazole as interference. The methods under study are area under the curve, simultaneous equation in addition to smart signal processing techniques of manipulating ratio spectra namely Savitsky-Golay filters and continuous wavelet transform. All the methods were validated according to the ICH guidelines where accuracy, precision and repeatability were found to be within the acceptable limits. The selectivity of the proposed methods was tested using laboratory prepared mixtures and assessed by applying the standard addition technique. So, they can therefore be used for the routine analysis of ciprofloxacin in quality-control laboratories.

  17. In Vitro Susceptibility of Iranian Isolates of Trichomonas vaginalis to Metronidazole

    PubMed Central

    MATINI, Mohammad; MAGHSOOD, Amir-Hossein; MOHEBALI, Mahdi; RABIEE, Soghra; FALLAH, Mohammad; REZAIE, Sassan; REZAEIAN, Mostafa

    2016-01-01

    Background: Metronidazole, a 5-nitroimidazole derivative, is the main antitrichomonal agent of choice for treatment of trichomoniasis. Since 1962, some cases of treatment failure with metronidazole have been reported and recently drug resistance is now on the rise in the world. This study was aimed to determine current susceptibility of Iranian isolates of Trichomonas vaginalis to metronidazole. Methods: This study was performed on 50 T. vaginalis isolates collected from west and central areas of Iran. After axenisation of the parasites, susceptibility testing was carried out by using serial twofold dilutions of metronidazole (400 to 0.1 μg/ml). The minimum inhibitory concentration (MIC) and the minimum lethal concentration (MLC) of the trichomonads were determined after 48 h incubation at 35.5 °C. Drug susceptibility assays of the all isolates were carried out two times in triplicate under aerobic and anaerobic conditions. Results: Ninety-eight percent of the T. vaginalis isolates (49/50) were sensitive to metronidazole. Metronidazole resistance was defined as aerobic MIC ≥50 μg/ml, detected in one isolate. The means of aerobic MICs and MLCs and that of anaerobic MICs of the parasites were 2.91, 1.95 and 0.28 μg/ml, respectively. Conclusion: This investigation showed in vitro low-level tolerance to metronidazole in a few T. vaginalis isolates that may be leading to the development of drug resistance. PMID:27095968

  18. Rifaximin therapy for metronidazole-unresponsive Clostridium difficile infection: a prospective pilot trial

    PubMed Central

    Patrick Basu, P.; Dinani, Amreen; Rayapudi, Krishna; Pacana, Tommy; Shah, Niraj James; Hampole, Hemant; Krishnaswamy, N. V.; Mohan, Vinod

    2010-01-01

    Background: Clostridium difficile infection (CDI) is a recent epidemic in the United States, particularly in the hospital setting. Oral metronidazole is standard therapy for C. difficile infection, but resistance to metronidazole is becoming a clinical challenge. Methods: We evaluated the efficacy of the nonsystemic oral antibiotic rifaximin for the treatment of metronidazole-resistant C. difficile infection. Twenty-five patients with C. difficile infection were enrolled in the study. All had mild-to-moderate C. difficile infection (5–10 bowel movements a day without sepsis) unresponsive to metronidazole (i.e. stools positive for toxins A and B after oral metronidazole 500 mg three times daily [t.i.d.] for 5 days). After discontinuation of metronidazole, rifaximin 400 mg t.i.d. for 14 days was prescribed. Patients were followed for 56 days and stool was tested for C. difficile using polymerase chain reaction (PCR) to assess the effect of treatment. A negative PCR test result was interpreted as a favorable response to rifaximin. Results: Sixteen of 22 patients (73%) were eligible for study inclusion and completed rifaximin therapy experienced eradication of infection (stool negative for C. difficile) immediately after rifaximin therapy and 56 days post-treatment. Three patients (12%) discontinued therapy because of abdominal distention. Rifaximin was generally well tolerated. Conclusions: In conclusion, rifaximin may be considered for treatment of mild-to-moderate C. difficile infection that is resistant to metronidazole. Larger randomized trials are needed to confirm these positive findings. PMID:21180604

  19. Broad-spectrum Antibiotic Plus Metronidazole May Not Prevent the Deterioration of Necrotizing Enterocolitis From Stage II to III in Full-term and Near-term Infants: A Propensity Score-matched Cohort Study.

    PubMed

    Luo, Li-Juan; Li, Xin; Yang, Kai-Di; Lu, Jiang-Yi; Li, Lu-Quan

    2015-10-01

    Necrotizing enterocolitis (NEC) is the most common and frequently dangerous neonatal gastrointestinal disease. Studies have shown broad-spectrum antibiotics plus anaerobic antimicrobial therapy did not prevent the deterioration of NEC among very low birth preterm infants. However, few studies about this therapy which focused on full-term and near-term infant with NEC has been reported. The aim of this study was to evaluate the effect of broad-spectrum antibiotic plus metronidazole in preventing the deterioration of NEC from stage II to III in full-term and near-term infants.A retrospective cohort study based on the propensity score (PS) 1:1 matching was performed among the full-term and near-term infants with NEC (Bell stage ≥II). All infants who received broad-spectrum antibiotics were divided into 2 groups: group with metronidazole treatment (metronidazole was used ≥4 days continuously, 15 mg/kg/day) and group without metronidazole treatment. The depraved rates of stage II NEC between the 2 groups were compared. Meanwhile, the risk factors associated with the deterioration of stage II NEC were analyzed by case-control study in the PS-matched cases.A total of 229 infants met the inclusion criteria. Before PS-matching, we found the deterioration of NEC rate in the group with metronidazole treatment was higher than that in the group without metronidazole treatment (18.1% [28/155] vs 8.1% [6/74]; P = 0.048). After PS-matching, 73 pairs were matched, and the depraved rate of NEC in the group with metronidazole treatment was not lower than that in the group without metronidazole treatment (15.1% vs 8.2%; P = 0.2). Binary logistic regression analysis showed that sepsis after NEC (odds ratio [OR] 3.748, 95% confidence interval [CI] 1.171-11.998, P = 0.03), the need to use transfusion of blood products after diagnosis of NEC (OR 8.003, 95% CI 2.365-27.087, P = 0.00), and the need of longer time for nasogastric suction were risk factors for stage II NEC progressing to

  20. Randomized pharmacokinetic and drug–drug interaction studies of ceftazidime, avibactam, and metronidazole in healthy subjects

    PubMed Central

    Das, Shampa; Li, Jianguo; Armstrong, Jon; Learoyd, Maria; Edeki, Timi

    2015-01-01

    We assessed pharmacokinetic and safety profiles of ceftazidime–avibactam administered ± metronidazole, and whether drug–drug interactions exist between ceftazidime and avibactam, or ceftazidime-avibactam and metronidazole. The first study (NCT01430910) involved two cohorts of healthy subjects. Cohort 1 received ceftazidime–avibactam (2000–500 mg) as a single infusion or as multiple intravenous infusions over 11 days to evaluate ceftazidime–avibactam pharmacokinetics. Cohort 2 received ceftazidime, avibactam, or ceftazidime–avibactam over 4 days to assess drug–drug interaction between ceftazidime and avibactam. The second study (NCT01534247) assessed interaction between ceftazidime–avibactam and metronidazole in subjects receiving ceftazidime–avibactam (2000–500 mg), metronidazole (500 mg), or metronidazole followed by ceftazidime–avibactam over 4 days. In all studies, subjects received a single-dose on the first and final days, and multiple-doses every 8 h on intervening days. Concentration-time profiles for ceftazidime and avibactam administered as single- or multiple-doses separately or together with/without metronidazole were similar. There was no evidence of time-dependent pharmacokinetics or accumulation. In both interaction studies, 90% confidence intervals for geometric least squares mean ratios of area under the curve and maximum plasma concentrations for each drug were within the predefined interval (80–125%) indicating no drug–drug interaction between ceftazidime and avibactam, or ceftazidime–avibactam and metronidazole. There were no safety concerns. In conclusion, pharmacokinetic parameters and safety of ceftazidime, avibactam, and metronidazole were similar after single and multiple doses with no observed drug–drug interaction between ceftazidime and avibactam, or ceftazidime–avibactam and metronidazole. PMID:26516584

  1. Pharmacokinetics of metronidazole in patients with varying degrees of renal failure.

    PubMed Central

    Houghton, G W; Dennis, M J; Gabriel, R

    1985-01-01

    Twenty-nine patients with varying degrees of renal insufficiency were given a single intravenous dose of metronidazole (500 mg). Plasma and urinary concentrations of metronidazole and two major metabolites were determined using a specific high performance liquid chromatographic assay. The pharmacokinetic parameters of metronidazole elimination half-life, area under the metronidazole concentration against time curve, apparent volume of distribution, metronidazole clearance and predicted degree of accumulation of metronidazole on repeated dosing were not statistically significantly affected by renal inadequacy of any degree. The urinary excretion of metronidazole in patients with moderate or severe renal insufficiency was approximately half the value in healthy volunteers. The renal clearance of metronidazole was significantly greater in healthy volunteers compared to renally insufficient patients, but accounted for less than 10% of the total metronidazole clearance in all groups. The elimination half-life and predicted accumulation (on three times daily dosing) of metabolite I [1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole] were significantly increased with decreasing renal function from 9.2 h and 2.3, respectively, in healthy volunteers to 34 h and 6.7, respectively, in patients with total renal failure. The degree of accumulation of this metabolite on repeated dosing is probably of limited clinical significance in all patients except those with severe or total renal failure for reasons detailed in the text. The elimination half-life and predicted accumulation on three times daily dosing of metabolite II, [2-methyl-5-nitroimidazole-1-acetic acid] increased rapidly with decreasing renal function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3986078

  2. Evaluation of Nitrofurantoin Combination Therapy of Metronidazole-Sensitive and -Resistant Helicobacter pylori Infections in Mice

    PubMed Central

    Jenks, Peter J.; Ferrero, Richard L.; Tankovic, Jacques; Thiberge, Jean-Michel; Labigne, Agnès

    2000-01-01

    The main objectives of this study were to determine whether the nitroreductase enzyme encoded by the rdxA gene of Helicobacter pylori was responsible for reductive activation of nitrofurantoin and whether a triple-therapy regimen with nitrofurantoin was able to eradicate metronidazole-sensitive and -resistant H. pylori infections from mice. The susceptibilities to nitrofurantoin of parent and isogenic rdxA mutant strains (three pairs), as well as a series of matched metronidazole-sensitive and -resistant strains isolated from mice (30) and patients (20), were assessed by agar dilution determination of the MIC. Groups of mice colonized with the metronidazole-sensitive H. pylori SS1 strain or a metronidazole-resistant rdxA SS1 mutant were treated with either metronidazole or nitrofurantoin as part of a triple-therapy regimen. One month after the completion of treatment the mice were sacrificed and their stomachs were cultured for H. pylori. The nitrofurantoin MICs for all strains tested were between 0.5 and 4.0 μg/ml. There was no significant difference between the susceptibility to nitrofurantoin of the parental strains and those of respective rdxA mutants or between those of matched metronidazole-sensitive and -resistant H. pylori isolates. The regimen with metronidazole eradicated infection from all eight SS1-infected mice and from one of eight mice inoculated with the rdxA mutant (P ≤ 0.001). The regimen with nitrofurantoin failed to eradicate infection from any of the six SS1-infected mice (P ≤ 0.001) and cleared infection from one of seven mice inoculated with the rdxA mutant. These results demonstrate that, despite the good in vitro activity of nitrofurantoin against H. pylori and the lack of cross-resistance between metronidazole and nitrofurantoin, eradication regimens involving nitrofurantoin are unable to eradicate either metronidazole-sensitive or -resistant H. pylori infections from mice. PMID:10991835

  3. Novel aryl carbamate derivatives of metronidazole as potential antiamoebic agents.

    PubMed

    Hayat, Faisal; Wahedi, Hussain Mustatab; Park, Seonghyeok; Tariq, Saba; Azam, Amir; Shin, Dongyun

    2016-01-01

    A series of novel aryl carbamate derivatives of metronidazole (MNZ) were designed, synthesized, and screened for antiamoebic activity. As compared to MNZ, most of the derivatives exhibited moderate to excellent activity against the HM1:IMSS strain of Entamoeba histolytica. Compounds 7, 14, 16, 19, and 21 exhibited the most promising antiamoebic activity with IC50 values of 0.24, 0.08, 0.26, 0.26, and 0.15 μM, respectively, compared to that of MNZ (1.78 μM). Moreover, from the toxicological studies of these compounds on human melanocytes, the melan-a cell line revealed that the potent compounds are nontoxic at concentrations ranging from 2.5 to 50 μM. PMID:26597858

  4. Mechanisms of selective toxicity of metronidazole and other nitroimidazole drugs.

    PubMed Central

    Edwards, D I

    1980-01-01

    The selectively toxic effect of nitroimidazole drugs towards anaerobic bacteria and protozoa depends on a number of factors. The killing action of such drugs as metronidazole requires the reduction of the nitro group, a process which influences the rate of entry of the drug into the susceptible cell and which is determined by mechanisms involving ferredoxin-linked (or the equivalent) reactions in the cell. The reduced agent subsequently causes strand breakage of DNA, the extent of which depends on the A + T content of the DNA. Other effects of such drugs may include the possible inhibition of DNA repair mechanisms which exacerbate DNA damage, Inhibition of activity of nitroimidazoles may be caused by aminothiol radical scavengers and radioprotectors normally present in the cell or by the presence of other organisms in the environment (that is, the vagina) capable of inactivating the drugs. PMID:7000306

  5. Severe hepatotoxicity associated with the combination of spiramycin plus metronidazole.

    PubMed

    Hussein, Rola; El-Halabi, Mustapha; Ghaith, Ola; Jurdi, Nawaf; Azar, Cecilio; Mansour, Nabil; Sharara, Ala I

    2011-03-01

    Drug-induced liver injury (DILI) is a leading cause of acute liver failure and is the most frequent reason for post-marketing drug withdrawal. The spectrum of liver injury is wide, ranging from mild and subclinical injury, noticeable only on routine biochemical testing, to fulminant liver failure and death. Antibiotics, as a group, are a leading cause of DILI. We herein describe 4 patients who developed moderate to severe hepatotoxicity after exposure to a commercially - available combination of two antibiotics - spiramycin and metronidazole - commonly used for the treatment and prevention of periodontal infections. No other aetiology for liver injury could be identified in all cases. Two patients recovered spontaneously, and two had a more severe course, one responding to corticosteroids and mycophenolate mofetil and the other requiring liver transplantation for subacute massive necrosis. PMID:21429456

  6. Broad-spectrum Antibiotic Plus Metronidazole May Not Prevent the Deterioration of Necrotizing Enterocolitis From Stage II to III in Full-term and Near-term Infants

    PubMed Central

    Luo, Li-Juan; Li, Xin; Yang, Kai-Di; Lu, Jiang-Yi; Li, Lu-Quan

    2015-01-01

    Abstract Necrotizing enterocolitis (NEC) is the most common and frequently dangerous neonatal gastrointestinal disease. Studies have shown broad-spectrum antibiotics plus anaerobic antimicrobial therapy did not prevent the deterioration of NEC among very low birth preterm infants. However, few studies about this therapy which focused on full-term and near-term infant with NEC has been reported. The aim of this study was to evaluate the effect of broad-spectrum antibiotic plus metronidazole in preventing the deterioration of NEC from stage II to III in full-term and near-term infants. A retrospective cohort study based on the propensity score (PS) 1:1 matching was performed among the full-term and near-term infants with NEC (Bell stage ≥II). All infants who received broad-spectrum antibiotics were divided into 2 groups: group with metronidazole treatment (metronidazole was used ≥4 days continuously, 15 mg/kg/day) and group without metronidazole treatment. The depraved rates of stage II NEC between the 2 groups were compared. Meanwhile, the risk factors associated with the deterioration of stage II NEC were analyzed by case-control study in the PS-matched cases. A total of 229 infants met the inclusion criteria. Before PS-matching, we found the deterioration of NEC rate in the group with metronidazole treatment was higher than that in the group without metronidazole treatment (18.1% [28/155] vs 8.1% [6/74]; P = 0.048). After PS-matching, 73 pairs were matched, and the depraved rate of NEC in the group with metronidazole treatment was not lower than that in the group without metronidazole treatment (15.1% vs 8.2%; P = 0.2). Binary logistic regression analysis showed that sepsis after NEC (odds ratio [OR] 3.748, 95% confidence interval [CI] 1.171–11.998, P = 0.03), the need to use transfusion of blood products after diagnosis of NEC (OR 8.003, 95% CI 2.365–27.087, P = 0.00), and the need of longer time for nasogastric suction were risk factors

  7. Properties of a new acid-buffering bioadhesive vaginal formulation (ACIDFORM).

    PubMed

    Garg, S; Anderson, R A; Chany, C J; Waller, D P; Diao, X H; Vermani, K; Zaneveld, L J

    2001-07-01

    Vaginal prophylactic methodology may prevent heterosexual transmission of the HIV and other sexually transmitted disease-causing organisms as well as unplanned pregnancies. A new delivery system (ACIDFORM) was designed with acid-buffering, bioadhesive, and viscosity-retaining properties to (1) maintain the acidic vaginal milieu (the low pH inactivates many pathogens and spermatozoa), (2) form a protective layer over the vaginal/cervical epithelium (minimizing contact with pathogenic organisms), and (3) provide long-term vaginal retention. A Phase I clinical study with ACIDFORM provided initial information about its safety and showed the formation of a layer over the vaginal/cervical epithelium [1; Amaral et al., Contraception 1999;60:361-6]. To study the properties of the gel (without active ingredient) in more detail, ACIDFORM's acid-buffering, bioadhesive, viscosity-retaining, and spermicidal properties were compared in vitro to marketed formulations, and its long-term stability was assessed. ACIDFORM, either when titrated with NaOH or when mixed directly with semen, is highly acid buffering and much more effective than Aci-Jel, a commercial acid-buffering vaginal product. ACIDFORM adheres well to two model membranes (excised sheep vagina and cellophane) and is more bioadhesive than Conceptrol, Advantage S, Replens, Aci-Jel, and K-Y jelly. On dilution, ACIDFORM also retains its viscosity better than these marketed products. ACIDFORM is spermicidal and is stable for at least 2 years. These results suggest that ACIDFORM has advantages over presently marketed vaginal delivery systems. The gel may either be useful by itself as an antimicrobial contraceptive product or as a formulation vehicle for an active ingredient with antimicrobial and/or contraceptive properties. PMID:11535216

  8. Enhanced amperometric detection of metronidazole in drug formulations and urine samples based on chitosan protected tetrasulfonated copper phthalocyanine thin-film modified glassy carbon electrode.

    PubMed

    Meenakshi, S; Pandian, K; Jayakumari, L S; Inbasekaran, S

    2016-02-01

    An enhanced electrocatalytic reduction of metronidazole antibiotic drug molecule using chitosan protected tetrasulfonated copper phthalocyanine (Chit/CuTsPc) thin-film modified glassy carbon electrode (GCE) has been developed. An irreversible reduction occurs at -0.47V (vs. Ag/AgCl) using Chit/CuTsPc modified GCE. A maximum peak current value is obtained at pH1 and the electrochemical reduction reaction is a diffusion controlled one. The detection limit is found to be 0.41nM from differential pulse voltammetry (DPV) method. This present investigation method is adopted for electrochemical detection of metronidazole in drug formulation and urine samples by using DPV method. PMID:26652358

  9. Optimization of a polymer composite employing molecular mechanic simulations and artificial neural networks for a novel intravaginal bioadhesive drug delivery device.

    PubMed

    Ndesendo, Valence M K; Pillay, Viness; Choonara, Yahya E; du Toit, Lisa C; Kumar, Pradeep; Buchmann, Eckhart; Meyer, Leith C R; Khan, Riaz A

    2012-01-01

    This study aimed at elucidating an optimal synergistic polymer composite for achieving a desirable molecular bioadhesivity and Matrix Erosion of a bioactive-loaded Intravaginal Bioadhesive Polymeric Device (IBPD) employing Molecular Mechanic Simulations and Artificial Neural Networks (ANN). Fifteen lead caplet-shaped devices were formulated by direct compression with the model bioactives zidovudine and polystyrene sulfonate. The Matrix Erosion was analyzed in simulated vaginal fluid to assess the critical integrity. Blueprinting the molecular mechanics of bioadhesion between vaginal epithelial glycoprotein (EGP), mucin (MUC) and the IBPD were performed on HyperChem 8.0.8 software (MM+ and AMBER force fields) for the quantification and characterization of correlative molecular interactions during molecular bioadhesion. Results proved that the IBPD bioadhesivity was pivoted on the conformation, orientation, and poly(acrylic acid) (PAA) composition that interacted with EGP and MUC present on the vaginal epithelium due to heterogeneous surface residue distributions (free energy= -46.33 kcalmol(-1)). ANN sensitivity testing as a connectionist model enabled strategic polymer selection for developing an IBPD with an optimally prolonged Matrix Erosion and superior molecular bioadhesivity (ME = 1.21-7.68%; BHN = 2.687-4.981 N/mm(2)). Molecular modeling aptly supported the EGP-MUC-PAA molecular interaction at the vaginal epithelium confirming the role of PAA in bioadhesion of the IBPD once inserted into the posterior fornix of the vagina. PMID:21231902

  10. Evaluation of metronidazole nanofibers in patients with chronic periodontitis: A clinical study

    PubMed Central

    Chaturvedi, Thakur Prasad; Srivastava, Ruchi; Srivastava, Anand Kumar; Gupta, Varun; Verma, Pushpendra Kumar

    2012-01-01

    Aim: Prevention of periodontal disease progression is the primary goal of periodontal therapy. When conventional therapy is found to be inadequate in achieving periodontal health in chronic periodontitis, local antimicrobial agents are used as an adjunct to scaling and root planing (SRP), which produces encouraging results. In the present study, an attempt was made to develop a low-dose controlled-release delivery system for the treatment of periodontal infections. A new sustained release drug system of poly e-caprolactone (PCL) nanofibers containing metronidazole (MET) was successfully electrospun and evaluated clinically for periodontal diseases. The retentive nanofibres were shown to provide a controlled delivery of the drugs. Materials and Methods: Nanofibers were prepared with MET in PCL by electrospinning technique. The drug-coated nanofibers provided sustained effect up to a period of 11 days (264 h) and followed first-order release. Forty sites in seven patients (four females and three males) with chronic periodontitis (5–8 mm probing depth) were allocated in two experimental treatment groups: Group A treated with SRP + MET nanofibers and Group B treated with SRP alone (control group). All these patients were evaluated clinically for probing depth (PD), plaque index (PI), and gingival index (GI). Results: Both the treatment groups were found to be efficacious in the treatment of periodontal disease as demonstrated by improvement in PD, PI, and GI. Conclusion: Combination of SRP + MET nanofibers (Group A) resulted in added benefits, compared to the control group. PMID:23580938

  11. ASSOCIATION OF CALCIUM HYDROXIDE AND METRONIDAZOLE IN THE TREATMENT OF DOG'S TEETH WITH CHRONIC PERIAPICAL LESION

    PubMed Central

    Panzarini, Sônia Regina; Souza, Valdir; Holland, Roberto; Dezan, Eloi

    2006-01-01

    One of the primary objectives of endodontic treatment of teeth with pulp necrosis is the elimination of microorganisms from the root canal system, as effectively as possible, especially in cases with chronic periapical lesions. AIM: The purpose of this study was to analyze the response of the periapical tissue of dogs' teeth with chronic periapical lesions to endodontic treatment performed with utilization of metronidazole, calcium hydroxide, and an association of both as root canal dressings. METHODOLOGY: Forty root canals were submitted to pulpectomy and the root canals were kept exposed to the oral environment for 6 months. Then, they were submitted to biomechanical preparation and divided into 4 study groups with 10 specimens: group I – no root canal dressing; group II – calcium hydroxide; group III – metronidazole; group IV – calcium hydroxide associated to metronidazole. After 15 days, the root canals were filled with Fill Canal sealer. After 90 days, the animals were killed and the especimens processed for histological analysis. RESULTS: Calcium hydroxide dressing provided a significantly better outcome compared to other experimental groups (α = 0.01). Also, the results of the association of metronidazole and calcium hydroxide were similar to those observed for the metronidazole group. The worst results were obtained by the no root canal dressing group. CONCLUSION: The use of metronidazole alone or associated with Calcium hydroxide, did not improve periapical healing when compared to Calcium hydroxide dressing. PMID:19089054

  12. A comparative clinical trial of albendazole versus metronidazole in children with giardiasis.

    PubMed

    Misra, P K; Kumar, A; Agarwal, V; Jagota, S C

    1995-07-01

    The adverse effects and treatment failures to some of the currently recommended drugs for giardia infection have given rise to the need for alternative antigiardial agents. In an open, randomized parallel group study, the safety and efficacy of albendazole was compared with metronidazole for the treatment of giardiasis in children. Sixty four children of age ranging from 2-12 years was randomized to receive either albendazole suspension 400 mg daily for 5 days or metronidazole suspension 400 mg daily for 5 days or metronidazole suspension 7.5 mg/Kg thrice daily for 5 days. The mean days required for cure, as evident by absence of cysts and/or trophozoites in the stool specimen, were 3.7 +/- 1.4 and 4.5 +/- 1.1 days, respectively for children on albendazole and metronidazole therapy. Six children on metronidazole therapy developed anorexia 2 to 4 days after the treatment. Albendazole proved as effective as metronidazole in the treatment of giardia infection in children with the added advantage of the absence of anorexia. PMID:8617554

  13. Development of a Curcumin Bioadhesive Monolithic Tablet for Treatment of Vaginal Candidiasis.

    PubMed

    Hani, Umme; Shivakumar, H G; Osmani, Riyaz Ali M; Srivastava, Atul; Kumar Varma, Naga Sravan

    2016-01-01

    The present investigation was designed to formulate a natural tablet for the treatment of vaginal candidiasis in order to eliminate side effects that are caused by existing antifungal drugs. Curcumin has promising antifungal activity in comparison with the existing azole antifungal drugs. Bioadhesive curcumin vaginal tablets were prepared by direct compression with different ratios of biadhesive polymers like xanthan gum, guar gum and HPMC. Curcumin tablets were characterized by studies of friability, hardness, hydration, DSC, mucoadhesion, In-vitro release and antifungal activity. DSC and FT-IR data indicate there was no interaction between the drug and the excipients and also polymer concentration has some effects on melting point of curcumin. Formulation F3 showed the best results in terms of swelling and mucoadhesion together with prolonged drug release. The antifungal activity of the Curcumin tablet has demonstrated a significant effect against Candida albicans. Hence, the study indicates the possible and effective use of curcumin bioadhesive monolithic vaginal tablet for vaginal candidiasis as a promising natural antifungal treatment. PMID:27610145

  14. Development of a Curcumin Bioadhesive Monolithic Tablet for Treatment of Vaginal Candidiasis

    PubMed Central

    Hani, Umme; Shivakumar, H.G.; Osmani, Riyaz Ali M.; Srivastava, Atul; Kumar Varma, Naga Sravan

    2016-01-01

    The present investigation was designed to formulate a natural tablet for the treatment of vaginal candidiasis in order to eliminate side effects that are caused by existing antifungal drugs. Curcumin has promising antifungal activity in comparison with the existing azole antifungal drugs. Bioadhesive curcumin vaginal tablets were prepared by direct compression with different ratios of biadhesive polymers like xanthan gum, guar gum and HPMC. Curcumin tablets were characterized by studies of friability, hardness, hydration, DSC, mucoadhesion, In-vitro release and antifungal activity. DSC and FT-IR data indicate there was no interaction between the drug and the excipients and also polymer concentration has some effects on melting point of curcumin. Formulation F3 showed the best results in terms of swelling and mucoadhesion together with prolonged drug release. The antifungal activity of the Curcumin tablet has demonstrated a significant effect against Candida albicans. Hence, the study indicates the possible and effective use of curcumin bioadhesive monolithic vaginal tablet for vaginal candidiasis as a promising natural antifungal treatment. PMID:27610145

  15. Buccal delivery of metformin: TR146 cell culture model evaluating the use of bioadhesive chitosan discs for drug permeability enhancement.

    PubMed

    Sander, Camilla; Nielsen, Hanne Mørck; Jacobsen, Jette

    2013-12-31

    The oral cavity is considered an attractive site of drug administration. Metformin is currently, used in oral diabetes treatment. The aim of the current study was to study the feasibility of metformin, to permeate the buccal epithelium applying a bioadhesive and permeation enhancing drug delivery system. The in vitro TR146 cell culture model was used to study the effect of drug concentration (5-100mM) and the impact of a bioadhesive chitosan formulation (discs) and chitosan in solution (0-20mg/mL) acting as a permeation enhancer. The permeation of metformin occurred by passive diffusion via the paracellular pathway driven by the concentration gradient, yet with a possibility of increasing the metformin transport by using higher, donor concentrations. When using floating baskets, as a new application of the TR146 cell culture model, it was possible to observe a time-dependent effect of the bioadhesive metformin discs and, metformin permeation may be increased due to a combination of bioadhesion and permeation enhancement induced by chitosan, although the permeation enhancing effect of chitosan was not statistically significant. The limited apparent buccal permeability of metformin observed in vitro, suggest that in vivo absorption of therapeutic doses of metformin needs to take place as a combination of buccal and intestinal absorption as metformin therapy requires the use of high doses. PMID:24148665

  16. Design and evaluation of an innovative floating and bioadhesive multiparticulate drug delivery system based on hollow structure.

    PubMed

    Zhang, Chungang; Tang, Jingya; Liu, Dechun; Li, Xuetao; Cheng, Lan; Tang, Xing

    2016-04-30

    In this study a gastric-retentive delivery system was prepared by a novel method which is reported here for the first time. An innovative floating and bioadhesive drug delivery system with a hollow structure was designed and prepared. The floating and bioadhesive drug delivery system was composed of a hollow spherical shell, a waterproof layer (Stearic acid), a drug layer (Ofloxacin), a release retarding film (the novel blended coating materials) and a bioadhesive layer (Carbomer 934P) prepared by using a liquid multi-layering process. A novel blended coating material was designed and investigated to solve the problem of the initial burst release of the formulation and the release mechanism of the novel material was analyzed in this study. The optimized formulation provided the sustained release characteristic and was able to float for 24h. The SEM cross-section images showed that the particulates were hollow with a spherical shell. X-ray images and pharmacokinetic studies (Frel = 124.1 ± 28.9%) in vivo showed that the gastric-retentive delivery system can be retained in the stomach for more than 6h. The floating and bioadhesive particulate drug delivery system based on a hollow structure with a dual function presented here is a viable alternative to other for gastroretentive drug delivery system. PMID:26943975

  17. Comparison of salivary fluoride concentrations after administration of a bioadhesive slow-release tablet and a conventional fluoride tablet.

    PubMed

    Bottenberg, P; Cleymaet, R; de Muynck, C; Remon, J P; Coomans, D; Slop, D

    1992-08-01

    The in-vitro and in-vivo fluoride release of bioadhesive, slow-release tablets prepared from a mixture of polyethylene glycol polymers, containing 0.1 mg of fluoride as NaF was studied, and their ability to sustain fluoride levels in saliva were compared with conventional fluoride tablets with the same fluoride content. In-vitro release experiments showed that the bioadhesive tablets needed 8 h to release all their fluoride compared with less than 1 h for the conventional fluoride tablets. In-vivo, the bioadhesive tablets had a retention period of 6 h and could sustain a salivary fluoride level of more than 10 microM above the baseline for 7 h. The conventional fluoride tablets achieved a peak concentration of 0.5 mM directly after dissolution in the mouth, but the fluoride level could not be sustained for longer than 1 h. A good agreement was found between the in-vitro swelling behaviour of the bioadhesive tablets and their in-vitro and in-vivo release characteristics and their in-vivo retention time. PMID:1359097

  18. Detection of Entamoeba histolytica DNA in the Saliva of Amoebic Liver Abscess Patients Who Received Prior Treatment with Metronidazole

    PubMed Central

    Khairnar, Krishna; Parija, Subhash Chandra

    2008-01-01

    Saliva is an easily-accessible and a non-invasive clinical specimen alternate to blood and liver pus. An attempt was made to detect Entamoeba histolytica DNA released in the saliva of amoebic liver abscess (ALA) patients by applying 16S-like rRNA gene-based nested multiplex polymerase chain reaction (NM-PCR). The NM-PCR detected E. histolytica DNA in the saliva of eight (28.6%) of 28 ALA patients. The NM-PCR result was negative for E. histolytica DNA in the saliva of all the eight ALA patients who were tested prior to treatment with metronidazole but was positive in the saliva of eight (40%) of 20 ALA patient who were tested after therapy with metronidazole. The NM-PCR detected E. histolytica DNA in liver abscess pus of all 28 (100%) patients with ALA. The TechLab E. histolytica II enzyme-linked immunosorbent assay was positive for E. histolytica Gal/GalNAc lectin antigen in the liver abscess pus of 13 (46.4%) of the 28 ALA patients. The indirect haemagglutination (IHA) test was positive for anti-amoebic antibodies in the serum of 22 (78.6%) of the 28 ALA patients and 2 (5.7%) of 35 healthy controls. The present study, for the first time, demonstrates the release of E. histolytica DNA in the saliva of ALA patients by applying NM-PCR. PMID:19069620

  19. Detection of Entamoeba histolytica DNA in the saliva of amoebic liver abscess patients who received prior treatment with metronidazole.

    PubMed

    Khairnar, Krishna; Parija, Subhash Chandra

    2008-12-01

    Saliva is an easily-accessible and a non-invasive clinical specimen alternate to blood and liver pus. An attempt was made to detect Entamoeba histolytica DNA released in the saliva of amoebic liver abscess (ALA) patients by applying 16S-like rRNA gene-based nested multiplex polymerase chain reaction (NM-PCR). The NM-PCR detected E. histolytica DNA in the saliva of eight (28.6%) of 28 ALA patients. The NM-PCR result was negative for E. histolytica DNA in the saliva of all the eight ALA patients who were tested prior to treatment with metronidazole but was positive in the saliva of eight (40%) of 20 ALA patient who were tested after therapy with metronidazole. The NM-PCR detected E. histolytica DNA in liver abscess pus of all 28 (100%) patients with ALA. The TechLab E. histolytica II enzyme-linked immunosorbent assay was positive for E. histolytica Gal/GalNAc lectin antigen in the liver abscess pus of 13 (46.4%) of the 28 ALA patients. The indirect haemagglutination (IHA) test was positive for anti-amoebic antibodies in the serum of 22 (78.6%) of the 28 ALA patients and 2 (5.7%) of 35 healthy controls. The present study, for the first time, demonstrates the release of E. histolytica DNA in the saliva of ALA patients by applying NM-PCR. PMID:19069620

  20. Effect of MMX® mesalamine coadministration on the pharmacokinetics of amoxicillin, ciprofloxacin XR, metronidazole, and sulfamethoxazole: results from four randomized clinical trials

    PubMed Central

    Pierce, David; Corcoran, Mary; Martin, Patrick; Barrett, Karen; Inglis, Susi; Preston, Peter; Thompson, Thomas N; Willsie, Sandra K

    2014-01-01

    Background MMX® mesalamine is a once daily oral 5-aminosalicylic acid formulation, effective in induction and maintenance of ulcerative colitis remission. Patients on long-term mesalamine maintenance may occasionally require concomitant antibiotic treatment for unrelated infections. Aim To evaluate the potential for pharmacokinetic interactions between MMX mesalamine and amoxicillin, ciprofloxacin extended release (XR), metronidazole, or sulfamethoxazole in four open-label, randomized, placebo-controlled, two-period crossover studies. Methods In all four studies, healthy adults received placebo once daily or MMX mesalamine 4.8 g once daily on days 1–4 in one of two treatment sequences. In studies 1 and 2, subjects also received a single dose of amoxicillin 500 mg (N=62) or ciprofloxacin XR 500 mg (N=30) on day 4. In studies 3 and 4, subjects received metronidazole 750 mg twice daily on days 1–3 and once on day 4 (N=30); or sulfamethoxazole 800 mg/trimethoprim 160 mg twice daily on days 1–3 and once on day 4 (N=44). Results MMX mesalamine had no significant effects on systemic exposure to amoxicillin, ciprofloxacin, or metronidazole; the 90% confidence intervals (CIs) around the geometric mean ratios (antibiotic + MMX mesalamine: antibiotic + placebo) for maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) fell within the predefined equivalence range (0.80–1.25). Sulfamethoxazole exposure increased by a statistically significant amount when coadministered with MMX mesalamine; however, increased exposure (by 12% in Cmax at steady state; by 15% in AUC at steady state) was not considered clinically significant, as the 90% CIs for each point estimate fell entirely within the predefined equivalence range. Adverse events in all studies were generally mild. Conclusion MMX mesalamine may be coadministered with amoxicillin, ciprofloxacin, metronidazole, or sulfamethoxazole, without affecting pharmacokinetics or safety of

  1. Preparation of multiple-unit floating-bioadhesive cooperative minitablets for improving the oral bioavailability of famotidine in rats.

    PubMed

    Zhu, Xuehua; Qi, Xiaole; Wu, Zhenghong; Zhang, Ziwei; Xing, Jiayu; Li, Xiangbo

    2014-09-01

    Abstract The aims of this study were to prepare fine famotidine-containing floating-bioadhesive cooperative minitablets and to investigate the possibility of using those minitablets as a delivery system for promoting the oral bioavailability of famotidine. Nine minitablet formulations were designed using hydroxypropylmethylcellulose (HPMC K4M) as release-retarding polymers, Carbopol 971P as bioadhesive materials and sodium bicarbonate (NaHCO3) as gas formers. The prepared 3 ± 0.02 mm minitablets were evaluated in terms of their swelling ability, floating behavior, bioadhesion test and in vitro release. The optimized minitablets (F6) containing HPMC K4M (50.00%, w/w), Carbopol 971P (10.00%, w/w) and NaHCO3 (10.00%, w/w) were found to float in 1 min and remain lastingly buoyant over a period of 8 h in vitro, with excellent bioadhesive properties (20.81 g) and sustained drug release characteristics (T50% = 46.54%) followed one-order model. In addition, plasma concentration-time profiles from pharmacokinetic studies in rats dosed with minitablets showed 1.62-fold (p < 0.05) increased absorption of famotidine, compared to the market tablets XinFaDing®. These studies demonstrated that the multiple-unit floating-bioadhesive cooperative minitablets may be a promising gastro-retentive delivery system for drugs that play a therapeutic role in the stomach. PMID:24456044

  2. Planar bioadhesive microdevices: a new technology for oral drug delivery

    PubMed Central

    Fox, Cade B.; Chirra, Hariharasudhan D.; Desai, Tejal A.

    2014-01-01

    The oral route is the most convenient and least expensive route of drug administration. Yet, it is accompanied by many physiological barriers to drug uptake including low stomach pH, intestinal enzymes and transporters, mucosal barriers, and high intestinal fluid shear. While many drug delivery systems have been developed for oral drug administration, the physiological components of the gastro intestinal tract remain formidable barriers to drug uptake. Recently, microfabrication techniques have been applied to create micron-scale devices for oral drug delivery with a high degree of control over microdevice size, shape, chemical composition, drug release profile, and targeting ability. With precise control over device properties, microdevices can be fabricated with characteristics that provide increased adhesion for prolonged drug exposure, unidirectional release which serves to avoid luminal drug loss and enhance drug permeation, and protection of a drug payload from the harsh environment of the intestinal tract. Here we review the recent developments in microdevice technology and discuss the potential of these devices to overcome unsolved challenges in oral drug delivery. PMID:25219863

  3. Prophylactic treatment with a novel bioadhesive gel formulation containing aciclovir and tenofovir protects from HSV-2 infection

    PubMed Central

    Shankar, Gita N.; Alt, Carsten

    2014-01-01

    Objectives Over-the-counter access to an inexpensive, effective topical microbicide could reduce the transmission of HIV and would increase women's control over their health and eliminate the need to obtain their partners' consent for prophylaxis. Chronic infection with herpes simplex virus 2 (HSV-2), also known as human herpes virus 2, has been shown to facilitate HIV infection and speed the progression to immunodeficiency disease. Our objective is to develop a drug formulation that protects against both HSV-2 and HIV infection and adheres to the vaginal surface with extended residence time. Methods We developed a formulation using two approved antiviral active pharmaceutical ingredients, aciclovir and tenofovir, in a novel bioadhesive vaginal delivery platform (designated SR-2P) composed of two polymers, poloxamer 407 NF (Pluronic® F-127) and polycarbophil USP (Noveon® AA-1). The efficacy of the formulation to protect from HSV-2 infection was tested in vitro and in vivo. In addition to its efficacy, it is essential for a successful microbicide to be non-irritating to the vaginal mucosa. We therefore tested our SR-2P platform gel in the FDA gold-standard microbicide safety model in rabbits and also in a rat vaginal irritation model. Results Our studies indicated that SR-2P containing 1% aciclovir and 5% tenofovir protects (i) Vero cells from HSV-2 infection in vitro and (ii) mice from HSV-2 infection in vivo. Our results further demonstrated that SR-2P was not irritating in either vaginal irritation model. Conclusions We conclude that SR-2P containing aciclovir and tenofovir may be a suitable candidate microbicide to protect humans from vaginal HSV-2 infection. PMID:25139839

  4. Interaction of calcium sulfate with xanthan gum: effect on in vitro bioadhesion and drug release behavior from xanthan gum based buccal discs of buspirone.

    PubMed

    Jaipal, A; Pandey, M M; Abhishek, A; Vinay, S; Charde, S Y

    2013-11-01

    Bioadhesive polymers in buccal drug delivery systems play an important role in delivery of therapeutic drug molecules for local and systemic action. Xanthan gum, a GRAS listed natural polymer was used to design buccal discs of buspirone hydrochloride by direct compression method. Effect of calcium sulfate on bioadhesive and drug release behavior of xanthan gum buccal discs was studied. Varying amount of calcium sulfate (0%, 5%, 10%, 20%, 30%, 40% and 50%, w/w) in combination with xanthan gum was used to prepare buccal bioadhesive discs. Increase in calcium sulfate concentration resulted in faster drug release and decreased the bioadhesive strength of the designed discs. Further, in rheological evaluation it was observed that viscosity of xanthan gum gel reduces with increasing concentration of calcium sulfate. Compatibility of drug with various excipients was assessed using DSC and FTIR techniques. PMID:23907052

  5. PAMAM dendrimer generation 5-pluronic F127 nanofilm as a matrix for local metronidazole release.

    PubMed

    Dung, Tran Huu; Do, Le Thanh; Yoo, Hoon

    2013-07-01

    A series of dendrimer G5-pluronic F127 nanofilms (at 1:10, 1:20 and 1:30 mole ratios), loaded with various percent of metronidazole hydrochloride, were prepared by the drug deposition with/without gelatin coating. The nanostructural feature of dendrimer G5-pluronic F127 as a matrix for a sustained drug release was investigated by choosing metronidazole, an antibacterial and antiprotozoal drug as a model drug. The studies on surface morphology, polymer erosion and metronidazole release of the prepared nanofilms revealed unique surface morphology, low film erosion rate and long drug release time. The drug release and the erosion rate of nanofilm were slowed in acidic pH condition and the presence of saliva in medium. The nanofilm of G5-PF127 (1:30 mole ratio) coated with gelatin further prolonged metronidazole release showing G5-PF127 coated with 20% gelatin to be the best suited for a metronidazole release. The nanofilms were stable for up to 9 months at dried condition, while those stored at room temperature with 30% relative humidity were less stable. Our results show that PAMAM dendrimer G5-pluronic F127 nanofilm has a potential to serve as a matrix for the local drug delivery. PMID:23909144

  6. Liquid chromatographic assay for metronidazole and tinidazole: pharmacokinetic and metabolic studies in human subjects.

    PubMed Central

    Nilsson-Ehle, I; Ursing, B; Nilsson-Ehle, P

    1981-01-01

    We developed methods for measuring metronidazole, its two major metabolites, and tinidazole in serum and urine. After treatment of each sample with an equal volume of 5% perchloric acid, the drugs were separated by reverse-phase high-pressure liquid chromatography (retention times, 6 to 18 min). Quantitation was based on spectrometry at 320 nm. These assays were sensitive, rapid, and specific, and recoveries from biological samples were quantitative. Metronidazole and tinidazole were given as rapid intravenous infusions to four healthy human volunteers. The biological half-lives of these two compounds were 5.4 and 11.1 h, respectively. The hydroxy metabolite of metronidazole appeared quickly in serum and was eliminated at a slow rate. The acetic acid metabolite of metronidazole was detected in serum at very low levels and only for a limited time. No metabolic products of tinidazole were found in serum samples. In urine, 43.7% of the administered dose of metronidazole was recovered over a period of 24 h (24.1% of the dose as the hydroxy metabolite, 12.0% as the acetic acid metabolite, and 7.6% as unchanged drug). Only 18.4% of the infused dose of tinidazole was eliminated in urine over a period of 72 h, and no metabolic products were detected. PMID:7294765

  7. Pharyngo-cutaneous fistulae after laryngectomy. Influence of previous radiotherapy and prophylactic metronidazole

    SciTech Connect

    Johansen, L.V.; Overgaard, J.; Elbrond, O.

    1988-02-15

    The development of a pharyngocutaneous fistulae is a major complication after total laryngectomy. In Denmark radiotherapy is the primary treatment for all laryngeal carcinomas. Based on the experience with conventional daily irradiation, a split-course radiation schedule was introduced in 1978. The charts of 106 consecutive patients laryngectomized for recurrence in the years 1975 to 1984 were examined. Thirty-four patients developed a fistula. An evaluation of the different radiotherapy schedules used during this period allowed a dose-response curve to be constructed. It showed a pronounced increase of fistulae with high doses of radiotherapy. Split-course radiotherapy caused a rise in late complications and did not improve tumor control. Large field sizes increased the number of fistulae. High-dose fractions showed a surprisingly high incidence of late complications. Prophylactic metronidazole (introduced in 1980) resulted in a highly significant decrease in the frequency of postoperative fistulae. Patients in whom fistula formed were hospitalized for an average of 54 days, patients without, for 22 days.

  8. Overall adsorption rate of metronidazole, dimetridazole and diatrizoate on activated carbons prepared from coffee residues and almond shells.

    PubMed

    Flores-Cano, J V; Sánchez-Polo, M; Messoud, J; Velo-Gala, I; Ocampo-Pérez, R; Rivera-Utrilla, J

    2016-03-15

    This study analyzed the overall adsorption rate of metronidazole, dimetridazole, and diatrizoate on activated carbons prepared from coffee residues and almond shells. It was also elucidated whether the overall adsorption rate was controlled by reaction on the adsorbent surface or by intraparticle diffusion. Experimental data of the pollutant concentration decay curves as a function of contact time were interpreted by kinetics (first- and second-order) and diffusion models, considering external mass transfer, surface and/or pore volume diffusion, and adsorption on an active site. The experimental data were better interpreted by a first-order than second-order kinetic model, and the first-order adsorption rate constant varied linearly with respect to the surface area and total pore volume of the adsorbents. According to the diffusion model, the overall adsorption rate is governed by intraparticle diffusion, and surface diffusion is the main mechanism controlling the intraparticle diffusion, representing >90% of total intraparticle diffusion. PMID:26731310

  9. Characterization and in vivo evaluation of ocular minitablets prepared with different bioadhesive Carbopol-starch components.

    PubMed

    Weyenberg, W; Bozdag, S; Foreman, P; Remon, J P; Ludwig, A

    2006-02-01

    The purpose of this study was to evaluate different bioadhesive ocular formulations based on drum dried waxy maize starch (DDWM), Amioca starch and Carbopol 974P. The concentrations of Carbopol 974P in the mixtures varied between 5 and 25% (w/w). The rheological properties of the non-sterilized and gamma-irradiated physical blends of Carbopol 974P with either DDWM or Amioca were compared to those of the corresponding co-spray dried Amioca starch/Carbopol powders. Higher viscosity or consistency values were measured for sterilized co-spray dried powder mixtures containing an amount of Carbopol 974P equal or above 15% (w/w) compared to the physical blends. Sustained release minitablets (2 mm, 6 mg), consisting of sodium fluorescein as model drug and the bioadhesive powders, were manufactured at a compression force of 1.25 kN. Afterwards, the tablets were sterilized with gamma-irradiation. The amount of Carbopol in the co-spray dried powder mixtures on the one hand and gamma-irradiation on the other hand had no significant influence on the crushing strength and friability of the minitablets evaluated. However, these two factors affected the in vitro release properties of the minitablets. The slowest release was obtained with tablets containing 25% Carbopol 974P, which unfortunately possess mucosal irritating properties. By using co-spray dried Amioca with 15% (w/w) Carbopol 974P, a slower release can be achieved compared to the physical mixtures of DDWM or Amioca starch with Carbopol 974P. Moreover, this ocular formulation is very promising and is preferred, as it did not cause any mucosal irritation and released the model drug for at least 12 h, after application in the fornix. PMID:16209917

  10. Quality analysis of salmon calcitonin in a polymeric bioadhesive pharmaceutical formulation: sample preparation optimization by DOE.

    PubMed

    D'Hondt, Matthias; Van Dorpe, Sylvia; Mehuys, Els; Deforce, Dieter; DeSpiegeleer, Bart

    2010-12-01

    A sensitive and selective HPLC method for the assay and degradation of salmon calcitonin, a 32-amino acid peptide drug, formulated at low concentrations (400 ppm m/m) in a bioadhesive nasal powder containing polymers, was developed and validated. The sample preparation step was optimized using Plackett-Burman and Onion experimental designs. The response functions evaluated were calcitonin recovery and analytical stability. The best results were obtained by treating the sample with 0.45% (v/v) trifluoroacetic acid at 60 degrees C for 40 min. These extraction conditions did not yield any observable degradation, while a maximum recovery for salmon calcitonin of 99.6% was obtained. The HPLC-UV/MS methods used a reversed-phase C(18) Vydac Everest column, with a gradient system based on aqueous acid and acetonitrile. UV detection, using trifluoroacetic acid in the mobile phase, was used for the assay of calcitonin and related degradants. Electrospray ionization (ESI) ion trap mass spectrometry, using formic acid in the mobile phase, was implemented for the confirmatory identification of degradation products. Validation results showed that the methodology was fit for the intended use, with accuracy of 97.4+/-4.3% for the assay and detection limits for degradants ranging between 0.5 and 2.4%. Pilot stability tests of the bioadhesive powder under different storage conditions showed a temperature-dependent decrease in salmon calcitonin assay value, with no equivalent increase in degradation products, explained by the chemical interaction between salmon calcitonin and the carbomer polymer. PMID:20655159

  11. Formulation development and evaluation of innovative two-polymer (SR-2P) bioadhesive vaginal gel.

    PubMed

    Podaralla, Satheesh; Alt, Carsten; Shankar, Gita N

    2014-08-01

    The main objective of this investigation was to study the feasibility of developing a vaginal bioadhesive microbicide using a SRI's proprietary two-polymer gel platform (SR-2P). Several formulations were prepared with different combinations of temperature-sensitive polymer (Pluronic® F-127) and mucoadhesive polymer (Noveon® AA-1), producing gels of different characteristics. Prototype polymeric gels were evaluated for pH, osmolality, buffering capacity, and viscosity under simulated vaginal semen dilutions, and bioadhesivity using ex vivo mini pig vaginal tissues and texture analyzer. The pH of the polymeric gel formulations ranged from 5.1 to 6.4; the osmolality varied from 13 to 173 mOsm. Absolute viscosity ranged from 513 to 3,780 cPs, and was significantly reduced (1.5- to 3-fold) upon incubation with simulated vaginal and semen fluid mixture. Among the tested gels (indicated in the middle row as a molar ratio of a mixture of Noveon vs. Pluronic), only SR-2P retained gel structure upon dilution with simulated fluids and mild simulated coital stress. The pH of the SR-2P gel was maintained at about 4.6 in simulated vaginal fluid and also showed high peak force of adhesion in mini pig vaginal tissue. Furthermore, SR-2P gel caused no or only minimal irritation in a mouse vaginal irritation model. The results of this preliminary study demonstrated the potential application of SR-2P gel as a vaginal microbicide vehicle for delivery of anti-HIV agents. PMID:24781671

  12. Discriminatory bio-adhesion over nano-patterned polymer brushes

    NASA Astrophysics Data System (ADS)

    Gon, Saugata

    Surfaces functionalized with bio-molecular targeting agents are conventionally used for highly-specific protein and cell adhesion. This thesis explores an alternative approach: Small non-biological adhesive elements are placed on a surface randomly, with the rest of the surface rendered repulsive towards biomolecules and cells. While the adhesive elements themselves, for instance in solution, typically exhibit no selectivity for various compounds within an analyte suspension, selective adhesion of targeted objects or molecules results from their placement on the repulsive surface. The mechanism of selectivity relies on recognition of length scales of the surface distribution of adhesive elements relative to species in the analyte solution, along with the competition between attractions and repulsions between various species in the suspension and different parts of the collecting surface. The resulting binding selectivity can be exquisitely sharp; however, complex mixtures generally require the use of multiple surfaces to isolate the various species: Different components will be adhered, sharply, with changes in collector composition. The key feature of these surface designs is their lack of reliance on biomolecular fragments for specificity, focusing entirely on physicochemical principles at the lengthscales from 1 - 100 nm. This, along with a lack of formal patterning, provides the advantages of simplicity and cost effectiveness. This PhD thesis demonstrates these principles using a system in which cationic poly-L-lysine (PLL) patches (10 nm) are deposited randomly on a silica substrate and the remaining surface is passivated with a bio-compatible PEG brush. TIRF microscopy revealed that the patches were randomly arranged, not clustered. By precisely controlling the number of patches per unit area, the interfaces provide sharp selectivity for adhesion of proteins and bacterial cells. For instance, it was found that a critical density of patches (on the order of

  13. Evaluation of early fetal exposure to vaginally-administered metronidazole in pregnant cynomolgus monkeys.

    PubMed

    Thompson, Kary E; Newcomb, Deanna L; Moffat, Graeme J; Zalikowski, Julie; Chellman, Gary J; McNerney, Mary Ellen

    2016-01-01

    Given concern about potential embryo-fetal harm following seminal exposure to drugs with teratogenic potential, pharmaceutical companies use theoretical calculations to estimate seminal concentrations, maternal exposure, and distribution across the placenta to the embryo-fetal compartment for risk assessment. However, it is plausible that there are additional mechanisms whereby the conceptus is exposed. In order to determine if theoretical calculations are sufficiently conservative to predict embryo-fetal exposure from drugs in semen, pregnant cynomolgus monkeys were given a vaginal dose of metronidazole during the early fetal period and cesarean-sectioned. Maternal, fetal, and amniotic fluid samples were analyzed for metronidazole and 2-hydroxymetronidazole. Exposure to metronidazole and its metabolite were comparable in all matrices. These data demonstrated no preferential transfer mechanism to conceptus following intravaginal administration of a small molecule drug; and therefore, suggest that traditional modeling for embryo-fetal exposure to drugs in semen in support of risk assessment for pharmaceutical agents is sufficiently conservative. PMID:26524246

  14. Metronidazole-containing gel for the treatment of periodontitis: an in vivo evaluation.

    PubMed

    Sato, Sandra; Fonseca, Maria José Vieira; Ciampo, José Orestes Del; Jabor, José Roberto; Pedrazzi, Vinícius

    2008-01-01

    The aim of this investigation was to monitor metronidazole concentrations in the gingival crevicular fluid (GCF) collected from periodontal pockets of dogs after treatment with an experimental 15% metronidazole gel. Five dogs had periodontitis induced by cotton ligatures placed subgingivally and maintained for a 30-day period. After the induction period, only pockets with 4 mm or deeper received the gel. Each pocket was filled up to the gingival margin by means of a syringe with a blunt-end needle. GCF was collected in paper strips and quantified in an electronic device before and after 15 minutes, 1 h, 6 h, 24 h and 48 h of gel administration. The GCF samples were assayed for metronidazole content by means of a high performance liquid chromatography method. Concentrations of metronidazole in the GCF of the 5 dogs (mean +/- SD, in microg/mL) were 0 +/- 0 before gel application and 47,185.75 +/- 24,874.35 after 15 minutes, 26,457.34 +/- 25,516.91 after 1 h, 24.18 +/- 23.11 after 6 h, 3.78 +/- 3.45 after 24 h and 3.34 +/- 5.54 after 48 h. A single administration of the 15% metronidazole gel released the drug in the GCF of dogs in levels several-fold higher than the minimum inhibitory concentration for some periodontopathogens grown in subgingival biofilms for up to one hour, but metronidazole could be detected in the GCF at least 48 hours after the gel application. PMID:18622484

  15. Biodegradable periodontal intrapocket device containing metronidazole and amoxycillin: formulation and characterisation.

    PubMed

    Ahuja, A; Ali, J; Rahman, S

    2006-01-01

    The purpose of the study was to formulate biodegradable intrapocket dental films, which could be easily placed into the periodontal pocket, and be capable of delivering therapeutic concentrations of amoxycillin and metronidazole for prolonged period of time with a much lower dose, hence obviating untoward side effects. A biodegradable intrapocket device containing amoxycillin and metronidazole was prepared using 69.29 mg each of amoxycillin and metronidazole, 2.0% diethyl phthalate plasticizer and 750 mg poly (L-lactide-co-glycolide). The device was optimized on the basis of evaluation parameters such as weight variation, content uniformity, surface pH, and in vitro and in vivo release studies. The films showed sustained in vitro release for a period of 16 days. In vivo release studies showed that drug concentrations were maintained above the MIC value for the entire period of the release studies. The samples from this study were capable of inhibiting the growth of most test strains. The combination of amoxycillin and metronidazole in the carrier polymer poly (L-lactide-co-glycolide) not only showed an extended spectrum of antimicrobial activity but also showed a synergistic effect against E. limosum, which had been reported the resistant to metronidazole in earlier studies. Stability studies were conducted on the optimized formulation and the degradation rate constant was found to be 4.6 x 10(-4)/day for metronidazole and 4.8 x 10-4)/day for amoxycillin. The drug was released locally and had a high benefit to low risk ratio as compared to systemic administration which is unacceptable due to, low benefit to high-risk ratio. Hence low-dose site-specific films present a better alternative. PMID:16454202

  16. Oral metronidazole, an effective treatment for Sweet's syndrome in a patient with associated inflammatory bowel disease.

    PubMed

    Banet, D E; McClave, S A; Callen, J P

    1994-09-01

    A 39-year-old woman with chronic, recurrent Sweet's syndrome (acute febrile neutrophilic dermatosis) and possible Crohn's disease was successfully treated with oral metronidazole. After 4 years of recurrent skin lesions which involved the hands and face, our patient developed genital and perianal ulcerations which were also histopathologically characterized by a neutrophilic infiltrate. In addition, she had a nondeforming polyarthritis that accompanied recurrences of her skin lesions. The patient was given oral metronidazole, an agent frequently used for perianal Crohn's disease, and achieved complete resolution of the perianal and perineal ulcers, the cutaneous lesions of Sweet's syndrome and the associated polyarthritis. PMID:7799365

  17. Zero order and signal processing spectrophotometric techniques applied for resolving interference of metronidazole with ciprofloxacin in their pharmaceutical dosage form.

    PubMed

    Attia, Khalid A M; Nassar, Mohammed W I; El-Zeiny, Mohamed B; Serag, Ahmed

    2016-02-01

    Four rapid, simple, accurate and precise spectrophotometric methods were used for the determination of ciprofloxacin in the presence of metronidazole as interference. The methods under study are area under the curve, simultaneous equation in addition to smart signal processing techniques of manipulating ratio spectra namely Savitsky-Golay filters and continuous wavelet transform. All the methods were validated according to the ICH guidelines where accuracy, precision and repeatability were found to be within the acceptable limits. The selectivity of the proposed methods was tested using laboratory prepared mixtures and assessed by applying the standard addition technique. So, they can therefore be used for the routine analysis of ciprofloxacin in quality-control laboratories. PMID:26540201

  18. Impact of metronidazole and amoxicillin combination on matrix metalloproteinases-1 and tissue inhibitors of matrix metalloproteinases balance in generalized aggressive periodontitis

    PubMed Central

    Cifcibasi, Emine; Kantarci, Alpdogan; Badur, Selim; Issever, Halim; Cintan, Serdar

    2015-01-01

    Objective: Generalized aggressive periodontitis (GAgP) is a complex periodontal disease affecting the entire dentition with a rapid destruction of the periodontium and resulting in loss of teeth. We hypothesized that better clinical healing of adjunctive use of amoxicillin plus metronidazole combination may be related to the effect of this combination therapy to restore imbalance between matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) which is associated with connective tissue and alveolar bone destruction in patients with GAgP. Materials and Methods: Twenty-eight subjects diagnosed with GAgP were recruited. Patients were randomly assigned to test or control groups. MMP-1/TIMP-1 ratio was compared between groups receiving scaling and root planning (SRP) alone (control) or in combination with amoxicillin plus metronidazole (test). Clinical periodontal variables were measured. Gingival crevicular fluid samples were obtained and analyzed for MMP-1 and TIMP-1. Measurements were taken at baseline and repeated at 3 and 6 months after therapy. Results: Total MMP-1 levels were significantly decreased in both groups (P < 0.05) at 3 and 6 months. MMP-1 concentration levels showed a similar pattern to MMP-1 total levels decreasing significantly at 3 months (P < 0.05). TIMP-1 concentration levels increased in the test group throughout the study period, while the difference did not reach statistical significance (P > 0.05). TIMP-1/MMP-1 balance was restored in test group at 6 months significantly better than the control group (P < 0.05). Conclusion: The results of this study suggest that metronidazole and amoxicillin combination as an adjunct to SRP results in better clinical healing through restoring TIMP-1/MMP-1 balance. PMID:25713485

  19. Draft Genome Sequence of a Metronidazole-Resistant Derivative of Gardnerella vaginalis Strain ATCC 14019

    PubMed Central

    Schuyler, Jessica A.; Mordechai, Eli; Adelson, Martin E.; Gygax, Scott E.

    2015-01-01

    We report the genome sequence of a metronidazole-resistant derivative of Gardnerella vaginalis ATCC 14019. This strain was obtained after serial selection to increase the MIC from 4 to ≥500 µg/ml. Two coding changes, in genes encoding a response regulator and an NAD+ synthetase, arose during selection. PMID:26564054

  20. A Reprofiled Drug, Auranofin, Is Effective against Metronidazole-Resistant Giardia lamblia

    PubMed Central

    Tejman-Yarden, Noa; Miyamoto, Yukiko; Leitsch, David; Santini, Jennifer; Debnath, Anjan; Gut, Jiri; McKerrow, James H.; Reed, Sharon L.

    2013-01-01

    Giardiasis is one of the most common causes of diarrheal disease worldwide. Treatment is primarily with 5-nitro antimicrobials, particularly metronidazole. Resistance to metronidazole has been described, and treatment failures can occur in up to 20% of cases, making development of alternative antigiardials an important goal. To this end, we have screened a chemical library of 746 approved human drugs and 164 additional bioactive compounds for activity against Giardia lamblia. We identified 56 compounds that caused significant inhibition of G. lamblia growth and attachment. Of these, 15 were previously reported to have antigiardial activity, 20 were bioactive but not approved for human use, and 21 were drugs approved for human use for other indications. One notable compound of the last group was the antirheumatic drug auranofin. Further testing revealed that auranofin was active in the low (4 to 6)-micromolar range against a range of divergent G. lamblia isolates representing both human-pathogenic assemblages A and B. Most importantly, auranofin was active against multiple metronidazole-resistant strains. Mechanistically, auranofin blocked the activity of giardial thioredoxin oxidoreductase, a critical enzyme involved in maintaining normal protein function and combating oxidative damage, suggesting that this inhibition contributes to the antigiardial activity. Furthermore, auranofin was efficacious in vivo, as it eradicated infection with different G. lamblia isolates in different rodent models. These results indicate that the approved human drug auranofin could be developed as a novel agent in the armamentarium of antigiardial drugs, particularly against metronidazole-resistant strains. PMID:23403423

  1. A comparative study of oral single dose of metronidazole, tinidazole, secnidazole and ornidazole in bacterial vaginosis

    PubMed Central

    Thulkar, Jyoti; Kriplani, Alka; Agarwal, Nutan

    2012-01-01

    Objective: To compare the cure rates of oral single dose of metronidazole (2 g), tinidazole (2 g), secnidazole (2 g), and ornidazole (1.5 g) in cases of bacterial vaginosis. Materials and Methods: This was a prospective, comparative, randomized clinical trial on 344 Indian women (86 women in each group) who attended a gynecology outpatient department with complaint of abnormal vaginal discharge or who had abnormal vaginal discharge on Gynecological examination but they did not complaint of it. For diagnosis and cure rate of bacterial vaginosis, Amsel's criteria were used. Statistical analysis was done by Chi-square test of proportions. The cure rate was compared considering metronidazole cure rate as gold standard. Results: At 1 week, the cure rate of tinidazole and ornidazole was 100% and at 4 weeks, it was 97.7% for both drugs (P<0.001). Secnidazole had cure rate of 80.2% at 4 weeks (P=NS). Metronidazole showed a cure rate of 77.9% at 4 weeks, which is the lowest of all four drugs. Conclusion: Tinidazole and ornidazole have better cure rate as compared to metronidazole in cases of bacterial vaginosis. PMID:22529484

  2. Metronidazole Vaginal Gel 1.3% in the Treatment of Bacterial Vaginosis: A Dose-Ranging Study

    PubMed Central

    Chavoustie, Steven E.; Jacobs, Mark; Reisman, Howard A.; Waldbaum, Arthur S.; Levy, Sharon F.; Hillier, Sharon L.; Nyirjesy, Paul

    2015-01-01

    Objective Metronidazole vaginal gel (MVG) 0.75% is a US Food and Drug Administration–approved, 5-day treatment for bacterial vaginosis (BV). This study tested the hypothesis that a shorter treatment course at a higher dose (MVG 1.3%) would yield similar efficacy to 5 days of MVG 0.75%. Materials and Methods This phase 2, multicenter, randomized, controlled, investigator-blinded, dose-ranging study enrolled women with a clinical diagnosis of BV. Patients were assigned to MVG 1.3% once daily for 1, 3, or 5 days or MVG 0.75% once daily for 5 days. The therapeutic cure rate, requiring clinical and bacteriological cure, at the end-of-study visit was determined for the per-protocol population. A Kaplan-Meier analysis was used to estimate median time-to-symptom resolution. Results In total, 255 women (mean age = 35 y) were enrolled. The per-protocol population included 189 patients. The therapeutic cure rate was higher in the 1-day (13/43, 30.2%), 3-day (12/48, 25.0%), and 5-day (16/49, 32.7%) MVG 1.3% groups versus the MVG 0.75% group (10/49, 20.4%). Median time-to-resolution of fishy odor was shorter in the 3 MVG 1.3% groups versus the MVG 0.75% group. The 5-day MVG 1.3% group had the lowest rate of symptom return. No clinically important differences were observed in adverse events across treatment groups; most events were mild or moderate in intensity and considered unrelated to treatment. Similar results were found in the modified intent-to-treat population. Conclusions Metronidazole vaginal gel 1.3% applied once daily for 1, 3, or 5 days showed similar efficacy, safety, and tolerability as MVG 0.75% once daily for 5 days. PMID:24983350

  3. Comparative Evaluation of Propolis, Metronidazole with Chlorhexidine, Calcium Hydroxide and Curcuma Longa Extract as Intracanal Medicament Against E.faecalis– An Invitro Study

    PubMed Central

    Nair, Rashmi; Asrani, Hemant

    2015-01-01

    Introduction The increase of potential side effects and safety concerns of conventional medicaments have led to the recent popularity of herbal alternative medications. The herbal products are known for its high antimicrobial activity, biocompatibility, anti-inflammatory and antioxidant properties. Aim The purpose of this study was to investigate and compare the effectiveness of Propolis, Metronidazole with Chlorhexidine gel, Curcuma Longa and Calcium Hydroxide for elimination of E.faecalis bacteria in extracted teeth samples. Materials and Methods Ninety extracted single rooted intact teeth were taken for the study. Decoronation, removal of apices and chemomechanical preparation was done for all samples. These sterilized samples were then contaminated with pure culture of E.faecalis under laminar flow. The samples were incubated for a period of 21 days. The infected samples were assigned to 5 groups: Group I- Propolis; Group II- Metronidazole with Chlorhexidine gel; Group III- Calcium hydroxide; Group IV- Curcuma Longa; and control group- Saline. Efficacy of newer intracanal medicaments against E.faecalis were carried out in the samples at the end of 1, 2 & 5 days for each group with the help of colorimeter. Student paired t-test, ANOVA and multiple tukey test were used for statistical analysis. Results The value of optical density was statistically significant in all groups when compared to that of control group. Group I (Propolis) produced better antimicrobial efficacy followed by Chlorhexidine Metronidazole combination, Curcuma Longa and Calcium hydroxide. Conclusion Within the limitations of this study, it can be concluded that Propolis showed better antimicrobial properties against E.faecalis than other medicaments. PMID:26673857

  4. Effect of Oral Administration of Metronidazole or Prednisolone on Fecal Microbiota in Dogs

    PubMed Central

    Ohno, Koichi; Horigome, Ayako; Odamaki, Toshitaka; Tsujimoto, Hajime

    2014-01-01

    Gastrointestinal microbiota have been implicated in the pathogenesis of various gastrointestinal disorders in dogs, including acute diarrhea and chronic enteropathy. Metronidazole and prednisolone are commonly prescribed for the treatment of these diseases; however, their effects on gastrointestinal microbiota have not been investigated. The objective of this study was to evaluate the effects of these drugs on the gastrointestinal microbiota of dogs. Metronidazole was administered twice daily at 12.5 mg/kg to a group of five healthy dogs, and prednisolone at 1.0 mg/kg daily to a second group of five healthy dogs for 14 days. Fecal samples were collected before and after administration (day 0 and 14), and 14 and 28 days after cessation (day 28 and 42). DNA was extracted, and the bacterial diversity and composition of each sample were determined based on 16S ribosomal RNA (rRNA) gene sequences using next-generation sequencing (Illumina MiSeq). In the group administered metronidazole, bacterial diversity indices significantly decreased at day 14, and recovered after the cessation. Principal coordinates analysis and hierarchical dendrogram construction based on unweighted and weighted UniFrac distance matrices revealed that bacterial composition was also significantly altered by metronidazole at day 14 compared with the other time points. The proportions of Bacteroidaceae, Clostridiaceae, Fusobacteriaceae, Lachnospiraceae, Ruminococcaceae, Turicibacteraceae, and Veillonellaceae decreased, while Bifidobacteriaceae, Enterobacteriaceae, Enterococcaceae, and Streptococcaceae increased at day 14 and returned to their initial proportions by day 42. Conversely, no effect of prednisolone was observed on either the bacterial diversity or composition. Reducing pathogenic bacteria such as Fusobacteria and increasing beneficial bacteria such as Bifidobacterium through the administration of metronidazole may be beneficial for promoting gastrointestinal health; however, further

  5. Effect of oral administration of metronidazole or prednisolone on fecal microbiota in dogs.

    PubMed

    Igarashi, Hirotaka; Maeda, Shingo; Ohno, Koichi; Horigome, Ayako; Odamaki, Toshitaka; Tsujimoto, Hajime

    2014-01-01

    Gastrointestinal microbiota have been implicated in the pathogenesis of various gastrointestinal disorders in dogs, including acute diarrhea and chronic enteropathy. Metronidazole and prednisolone are commonly prescribed for the treatment of these diseases; however, their effects on gastrointestinal microbiota have not been investigated. The objective of this study was to evaluate the effects of these drugs on the gastrointestinal microbiota of dogs. Metronidazole was administered twice daily at 12.5 mg/kg to a group of five healthy dogs, and prednisolone at 1.0 mg/kg daily to a second group of five healthy dogs for 14 days. Fecal samples were collected before and after administration (day 0 and 14), and 14 and 28 days after cessation (day 28 and 42). DNA was extracted, and the bacterial diversity and composition of each sample were determined based on 16S ribosomal RNA (rRNA) gene sequences using next-generation sequencing (Illumina MiSeq). In the group administered metronidazole, bacterial diversity indices significantly decreased at day 14, and recovered after the cessation. Principal coordinates analysis and hierarchical dendrogram construction based on unweighted and weighted UniFrac distance matrices revealed that bacterial composition was also significantly altered by metronidazole at day 14 compared with the other time points. The proportions of Bacteroidaceae, Clostridiaceae, Fusobacteriaceae, Lachnospiraceae, Ruminococcaceae, Turicibacteraceae, and Veillonellaceae decreased, while Bifidobacteriaceae, Enterobacteriaceae, Enterococcaceae, and Streptococcaceae increased at day 14 and returned to their initial proportions by day 42. Conversely, no effect of prednisolone was observed on either the bacterial diversity or composition. Reducing pathogenic bacteria such as Fusobacteria and increasing beneficial bacteria such as Bifidobacterium through the administration of metronidazole may be beneficial for promoting gastrointestinal health; however, further

  6. A Case Report of Metronidazole Induced Neurotoxicity in Liver Abscess Patient and the Usefulness of MRI for its Diagnosis

    PubMed Central

    Agarwal, Arjit; Shukla, Arvind; Joon, Pawan

    2016-01-01

    Metronidazole is a very widely used drug for the treatment of multiple ailments caused by anaerobic bacteria as well as some protozoan parasites. Though its usual side effects are not very serious, yet sometimes it may cause profound adverse effects like neurotoxicity. We present here a case of liver abscess. The patient was treated for a long time with metronidazole and developed sudden onset neurotoxicity which was diagnosed by MRI. The present case also highlights the need of vigilant monitoring of patients on metronidazole for symptoms of neurotoxicity and the usefulness of MRI for diagnosis of the same. PMID:26894145

  7. Evaluation of Epirubicin in Thermogelling and Bioadhesive Liquid and Solid Suppository Formulations for Rectal Administration

    PubMed Central

    Lo, Yu-Li; Lin, Yijun; Lin, Hong-Ru

    2014-01-01

    Temperature sensitive Pluronic (Plu) and pH-sensitive polyacrylic acid (PAA) were successfully mixed in different ratios to form in situ gelling formulations for colon cancer therapy. The major formulations were prepared as the liquid and solid suppository dosage forms. Epirubicin (Epi) was chosen as a model anticancer drug. In vitro characterization and in vivo pharmacokinetics and therapeutic efficacy of Epi in six Plu/PAA formulations were evaluated. Our in vitro data indicate that Epi in Plu 14%/PAA 0.75% of both solid and liquid suppositories possess significant cytotoxicity, strong bioadhesive force, long-term appropriate suppository base, sustained release, and high accumulation of Epi in rat rectums. These solid and liquid suppositories were retained in the upper rectum of Sprague-Dawley (SD) rats for at least 12 h. An in vivo pharmacokinetic study using SD rats showed that after rectal administration of solid and liquid suppositories, Epi had greater area under the curve and higher relative bioavailability than in a rectal solution. These solid and liquid suppositories exhibited remarkable inhibition on the tumor growth of CT26 bearing Balb/c mice in vivo. Our findings suggest that in situ thermogelling and mucoadhesive suppositories demonstrate a great potential as colon anticancer delivery systems for protracted release of chemotherapeutic agents. PMID:24384838

  8. Micelle-enhanced spectrofluorimetric determination of amlexanox in bioadhesive buccal tablets: application to content uniformity testing.

    PubMed

    Walash, M I; Belal, F; Tolba, M M; Halawa, M I

    2015-09-01

    A highly sensitive, simple and rapid spectrofluorimetric method was developed for the determination of Amlexanox (AMX) in its bioadhesive buccal tablets. The proposed method is based on measuring the native fluorescence of the methanolic solution of AMX at 400 nm after excitation at 242 nm in 0.2 M borate buffer (pH 10) and 0.5% w/v sodium dodecyl sulfate (SDS) solution. The interaction of AMX with SDS was studied, and the enhanced fluorescence intensity was exploited to develop an assay method for the determination of AMX. The relative fluorescence intensity-concentration plot was rectilinear over the range 5.0-80.0 ng/mL, with a lower detection limit of 0.57 ng/mL and a lower quantification limit of 1.74 ng/mL. The proposed method was successfully applied to the analysis of AMX in its commercial tablets. Moreover, content uniformity testing was conducted by applying official USP guidelines. Statistical evaluation and comparison of the data obtained using the proposed and comparison methods revealed good accuracy and precision for the proposed method. PMID:25611457

  9. Monitoring the Long-Term Degradation Behavior of Biomimetic Bioadhesive using Wireless Magnetoelastic Sensor

    PubMed Central

    Lin, Meng-Hsien; Anderson, Jonathan; Pinnaratip, Rattapol; Meng, Hao; Konst, Shari; DeRouin, Andrew J.; Rajachar, Rupak

    2015-01-01

    The degradation behavior of a tissue adhesive is critical to its ability to repair a wound while minimizing prolonged inflammatory response. Traditional degradation tests can be expensive to perform, as they require large numbers of samples. The potential for using magnetoelastic resonant sensors to track bioadhesive degradation behavior was investigated. Specifically, biomimetic poly(ethylene glycol)- (PEG-) based adhesive was coated onto magnetoelastic (ME) sensor strips. Adhesive-coated samples were submerged in solutions buffered at multiple pH levels (5.7, 7.4 and 10.0) at body temperature (37°C) and the degradation behavior of the adhesive was tracked wirelessly by monitoring the changes in the resonant amplitude of the sensors for over 80 days. Adhesive incubated at pH 7.4 degraded over 75 days, which matched previously published data for bulk degradation behavior of the adhesive while utilizing significantly less material (~103 times lower). Adhesive incubated at pH 10.0 degraded within 25 days while samples incubated at pH 5.7 did not completely degrade even after 80 days of incubation. As expected, the rate of degradation increased with increasing pH as the rate of ester bond hydrolysis is higher under basic conditions. As a result of requiring a significantly lower amount of samples compared to traditional methods, the ME sensing technology is highly attractive for fully characterizing the degradation behavior of tissue adhesives in a wide range of physiological conditions. PMID:26087077

  10. A novel vaginal drug delivery system: anti-HIV bioadhesive film containing abacavir.

    PubMed

    Ghosal, Kajal; Ranjan, Alok; Bhowmik, Benoy Brata

    2014-07-01

    Women are very much susceptible for acquired immunodeficiency syndrome (AIDS) and other sexually transmitted diseases (STDs), mainly due to unprotected heterosexual vaginal intercourse and for some other social and economical disadvantages. Our aim was to formulate and optimize vaginal film of abacavir, a potent nucleoside reverse transcriptase inhibitor, for the treatment of AIDS and HIV. Abacavir films were prepared by solvent evaporation method using sodium alginate (Na-alginate) as the main polymer, Hydroxypropyl Methylcellulose E 15 (HPMC E 15) as the copolymer and glycerol as a humectant. Abacavir sulphate (ABC) was used here as a drug. Films were optimized for various physicochemical parameters such as tensile strength, % elongation at break, swelling capacity, drug content (mg/cm(2)), thickness, folding endurance, bioadhesion, pH, moisture content and SEM. Drug polymer interaction was studied by FTIR Spectra. The drug release study was accomplished in dissolution apparatus. In vivo study was also carried out. This newly formed film was one kind of sustain release type and can be considered as a novel drug carrier system for the treatment of AIDS and other STDs. It was suitable for local as well as systemic effect. The films showed good physicochemical property with good aesthetic appeal. PMID:24699799

  11. Bioadhesive microdevices with multiple reservoirs: a new platform for oral drug delivery.

    PubMed

    Ahmed, Aamer; Bonner, Chris; Desai, Tejal A

    2002-06-17

    A variety of delivery systems have been devised, in recent years, to improve the oral bioavailability of drugs including enterically coated tablets, capsules, particles, and liposomes. Microfabrication technology may offer some potential advantages over conventional drug delivery technologies. This technology, combined with appropriate surface chemistry, may permit the highly localized and unidirectional release of drugs, permeation enhancers, and/or promoters. In this study, we demonstrate the fabrication of prototype reservoir-containing microdevices and a surface chemistry protocol that can be used to bind lectin via avidin-biotin interactions to these micromachined drug delivery vehicles. The use of microfabrication allows one to tailor the size, shape, reservoir volume, and surface characteristics of the drug delivery vehicle. In vitro studies show enhanced bioadhesion of these lectin conjugated silicon microdevices. This approach may be used to improve the absorption of pharmacologically active biopolymers such as peptides, proteins and oligonucleotides into circulation at targeted sites in the GI system via the creation of a robust hybrid organic/inorganic delivery system. This paper describes one of the first applications of microfabrication to oral drug delivery. PMID:12044568

  12. Novel bioadhesive hyaluronan-itaconic acid crosslinked films for ocular therapy.

    PubMed

    Calles, J A; Tártara, L I; Lopez-García, A; Diebold, Y; Palma, S D; Vallés, E M

    2013-10-15

    New hyaluronic acid (HA)-itaconic acid (IT) films have been previously synthesized and used as potential topical drug delivery systems (DDS) for ocular administration. In this study we explored homogeneous and heterogeneous crosslinking reactions of HA using glutaraldehyde (GTA) and polyethylene glycol diglycidyl ether (PEGDE) in the presence of IT, a naturally occurring compound that is non-toxic and readily biodegradable. We have studied the morphology, mechanical properties and in vitro biocompatibility between these new materials and ocular surface cells (human corneal epithelial cell line) and evaluated the biopharmaceutical performance of the designed formulations. Although all the synthesized materials exhibited good mechanical properties, the PEGDE modified films exhibited the best biocompatibility, with in vivo assays showing good adhesive performance and minimal irritation. PEGDE films were also tested for their effects in the treatment of intraocular pressure (IOP) in rabbits using timolol maleate (TM) as the model drug. These results may be useful for further design of novel bioadhesive matrix containing drugs by topical application in ophthalmology. PMID:23911915

  13. Development of hydrocolloid Bi-layer dressing with bio-adhesive and non-adhesive properties.

    PubMed

    Khan, M Iqbal H; Islam, Jahid M M; Kabir, Wasifa; Rahman, Ataur; Mizan, Maria; Rahman, M Fizur; Amin, Jakia; Khan, Mubarak A

    2016-12-01

    Bio-active bi-layer thin film having both bio-adhesive and non-adhesive end composed of polyvinyl alcohol (PVA) and gelatin/chitosan/polyethylene glycol (PEG) blend was developed for biomedical applications especially as an alternative of advanced tissue scaffold. The developed composite film was subjected to mechanical, thermal and physico-chemical characterization such as tensile strength (TS) and elongation at break (Eb), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), fluid drainage capacity and biocompatibility. Suitable packaging was also selected and stability study and aging test of the composite film were performed after packing. The incorporation of chitosan and PEG into gelatin showed improved mechanical properties of both TS and Eb, which suggested the occurrence of interaction among gelatin, chitosan and PEG molecules in the composite film. The presence of crosslinking as an interaction of above three polymers was also confirmed by FTIR study. Results from the DSC study suggested increased thermal stability after crosslinking. On the other hand, water uptake studies suggested excellent fluid drainage capability and hydro-stability of the composite film. The proposed dressing also showed excellent biocompatibility. Based on the studies related to the performance with confirmed identity, we concluded that our developed bi-layer film is very potential as an ideal wound dressing material. PMID:27612753

  14. Chemical Stability and Bioadhesive Properties of an Ester Prodrug of Δ9-Tetrahydrocannabinol in Poly (Ethylene Oxide) Matrices: Effect of Formulation Additives

    PubMed Central

    Thumma, Sridhar; Majumdar, Soumyajit; ElSohly, Mahmoud A.; Gul, Waseem; Repka, Michael A.

    2008-01-01

    The objective of the present research was to stabilize a novel hemiglutarate ester prodrug of Δ9-tetrahydrocannabinol (THC), in polyethylene oxide (PEO) polymeric matrices produced by hot-melt fabrication, for systemic delivery of THC through the oral transmucosal route. For this purpose, the influence of pH modifiers and antioxidants employed as stabilizing agents in these matrices was investigated. Based on the stability studies, two final formulations were made, and the stability of the active was assessed in these systems. In addition, the bioadhesive properties of PEO matrices were studied as a function of bioadhesive polymer type and concentration, contact time, drug loading and wetting time. Of all of the polymers investigated, bioadhesion was highest with Carbopol® 971p. Bioadhesion increased with bioadhesive polymer concentration and wetting time to a certain level beyond which there was no further contribution. Both the contact time and drug loading influenced the bioadhesion. Severe degradation of the prodrug was observed during storage, even at room temperature (75% at the end of 3 months). Incorporation of the stabilizing agents in the PEO matrices reduced the degradation of the prodrug considerably. Citric acid was the most effective of all of the pH modifiers studied. Among the various antioxidants utilized, degradation was observed least in presence of BHT and ascorbic acid. Only 7.6% and 8.2% of prodrug degraded in these matrices, respectively, as compared to the PEO only matrices (59.4%) at the end of 3 months at 25 °C/60% RH. The prodrug was very stable in both of the final formulations at the end of the 3 months at 40 °C/75% RH. PMID:18652884

  15. Ex vivo mucoadhesion and in vivo bioavailability assessment and correlation of ketoprofen tablet dosage forms containing bioadhesives.

    PubMed

    Zaghloul, A; Taha, E; Afouna, M; Khattab, I; Nazzal, S

    2007-05-01

    The purposes of this study were to assess the mucoadhesion and bioavailability and their correlation for ketoprofen tablet dosage forms (F1-F6) containing polycarbophil (PC), sodium carboxymethylcellulose (Na CMC) as bioadhesives, Avicel pH 101 as direct compressible tablet vehicle or mixtures of these, and non compressible vehicles such as lactose and starch. For mucoadhesion assessment, we used sheep gastric mucosa and for bioavailability we used six human volunteers in an open randomized seven-way crossover study. Young's modulus (YM) and relative bioavailability (RB) parameters were used for evaluation of mucoadhesion and bioavailability, respectively. The results indicated that F2 containing Na CMC (72.5%) showed the highest value of YM (7.6 +/- 0.76 pascals) and 119.4 +/- 3.2% for RB. Decreasing the amount of Na CMC to 10% in F3 and F6 decreased the values of YM and RB to 1.4 +/- 0.08 and 84 +/- 2.05 in F3, 4.6 +/- 0.43 and 114.7 +/- 2.46 in F6, respectively. The highest RB (152.3 +/- 2.56) was observed in F5 containing starch and Avicel pH 101. This formulation showed 6 +/- 0.87 for YM. F4 containing PC (10%) showed 5.1 +/- 0.43 and 74.15 +/- 1.98 for YM and RB respectively. The lowest value of YM was observed in F1 containing Avicel pH 101 (0.27 +/- 0.01) which also showed low RB (93.3 +/- 2.3). In conclusion, formulations containing bioadhesives and/or starch in high concentration showed high values of YM and RB which indicate good correlation between mucoadhesion and bioavailability. Bioadhesives may show a high potential to improve bioavailability and therapeutic efficacy of ketoprofen in tablet dosage forms. PMID:17557741

  16. Use of metronidazole as part of an empirical antibiotic regimen after incision and drainage of infections of the odontogenic spaces.

    PubMed

    Bali, Rishi; Sharma, Parveen; Gaba, Shivani

    2015-01-01

    The combination of amoxicillin/clavulanate and metronidazole is a widely-accepted empirical regimen for infections of the odontogenic spaces. Once adequate drainage has been established micro-organisms are less likely to grow and multiply, particularly anaerobes. This may obviate the need for anaerobic coverage after drainage in healthy hosts. We studied 60 patients in this randomised prospective study, the objective of which was to evaluate metronidazole as part of an empirical antibiotic regimen after drainage of infections of the odontogenic spaces. Samples of pus were sent for culture and testing for sensitivity. Amoxicillin/clavulanate and metronidazole were given to all patients. After incision and drainage the patients were randomly allocated to two groups. In the first group both antibiotics were continued, and in the second metronidazole was withdrawn. The groups were compared both clinically and microbiologically. There were no significant differences between the groups in the resolution of infection. Thirteen patients (n=6 in the 2-antimicrobial group, and n=7 in the amoxicillin/clavulanate group) showed no improvement during the 48 h postoperatively. Overall there was need to substitute another antibiotic for amoxicillin/clavulanate in only 6 cases. Six patients in the amoxicillin/clavulanate group required the addition of metronidazole after drainage. We conclude that in healthy subjects metronidazole is not necessary in the period after drainage, but its prescription should be based on assessment of clinical and laboratory markers of infection. PMID:25277645

  17. Metronidazole- and Carbapenem-Resistant Bacteroides thetaiotaomicron Isolated in Rochester, Minnesota, in 2014

    PubMed Central

    Sadarangani, Sapna P.; Cunningham, Scott A.; Jeraldo, Patricio R.; Wilson, John W.; Khare, Reeti

    2015-01-01

    Emerging antimicrobial resistance in members of the Bacteroides fragilis group is a concern in clinical medicine. Although metronidazole and carbapenem resistance have been reported in Bacteroides thetaiotaomicron, a member of the B. fragilis group, they have not, to the best of our knowledge, been reported together in the same B. thetaiotaomicron isolate. Herein, we report isolation of piperacillin-tazobactam-, metronidazole-, clindamycin-, ertapenem-, and meropenem-resistant B. thetaiotaomicron from a patient with postoperative intra-abdominal abscess and empyema. Whole-genome sequencing demonstrated the presence of nimD with at least a portion of IS1169 upstream, a second putative nim gene, two β-lactamase genes (one of which has not been previously reported), two tetX genes, tetQ, ermF, two cat genes, and a number of efflux pumps. This report highlights emerging antimicrobial resistance in B. thetaiotaomicron and the importance of identification and antimicrobial susceptibility testing of selected anaerobic bacteria. PMID:25941219

  18. Metronidazole: a method for its determination in biological fluids and its disposition kinetics in the dog.

    PubMed

    Neff-Davis, C A; Davis, L E; Gillette, E L

    1981-06-01

    A method for the analytical determination of metronidazole concentrations in biological tissues was developed using high performance liquid chromatography. The procedure was employed to investigate the pharmacokinetics of metronidazole in dogs following intravenous and oral administration (44 mg/kg). The overall elimination rate constant beta was 0.0027 +/- 0.0005 min-1, the apparent specific volume of distribution (V'd) was 0.948 +/- 0.096 L/kg overall clearance (ClB) was 2.49 +/- 0.54 ml/kg/min and the rate constant for absorption Kab was 0.0456 +/- 0.0353 min-1. Oral bioavailability was high but variable (59%-100%). Implications of these data for chemotherapy of infections caused by anaerobic bacteria, trichomonads, and Giardia and for the sensitization of hypoxic neoplastic cells to radiotherapy are discussed. PMID:7349324

  19. [Using Metronidazole and Hydroxyapatite for preventing dry socket after extraction of impacted mandibular 3rd molar

    PubMed

    Xue, Z X; Mao, T Q

    1993-03-01

    Dry socket is one of the most frequent complications after teeth extraction,especially in impacted mandibular third molars.The etilogy and prevention is not clear.This study id based on principles of clinical epidemiology.Randomized double-blind method was carried out in 549 patients to test the value of the prophylactic use of Hydroxyapatite,to test the value of the prophylactic use of Hydroxyapatite and Metronidazole,placed in the sockets of extracted impacted mandibular third molars.The results of the incidence of DS was 7.1% of Metronidazole treated sockets,and 2.1% of Hydroxyapatite treated sockets,It is concluded that Hydroxyapatite is an effective preventive factor for dry socket,The possible mechanism of Hydroxyapatite and the dry socket etiology were discussed. PMID:15159869

  20. The effect of metronidazole on the development of plaque and gingivitis in the beagle dog.

    PubMed

    Heijl, L; Lindhe, J

    1979-08-01

    The present investigation was performed in order to assess if the administration of metronidazole changed the composition of developing plaque in dogs, which at the start of the study were free from signs of gingivitis. Five beagle dogs were used. Throughout the observation period the animals were fed a diet which favored plaque accumulation. A baseline examination involved assessments of plaque, gingivitis and gingival exudate. Gingival biopsies were sampled and the tissue examined by a point counting procedure. The composition of the subgingival bacterial flora was assessed by dark-field microscopy. The bacteria were characterized into the following types: coccoid cells, straight rods, filaments, fusiforms, motile and curved rods and spirochetes. Following the baseline examination the teeth of the right jaws were allowed to accumulate plaque. A careful tooth cleaning program was maintained in the left jaw quadrants. Plaque and gingivitis assessments were repeated and biopsies sampled in the right jaws after 7, 14 and 28 days of no tooth cleaning. On experimental day 28 the second part of the study was initiated. A baseline examination was performed in the left jaws, after which the tooth cleaning program also in this part of the dentition was terminated. During the subsequent 28-day period each animal was given a dosage of 20 mg metronidazole/kilogram bodyweight/day. Clinical examinations and biopsies were repeated after 7, 14 and 28 days. The results demonstrated that metronidazole administered via the systemic route during a 28-day period can effectively decrease plaque and gingivitis development in dogs. The bacterial flora from subgingival sites of healthy gingiva was dominated by coccoid cells and straight rods. During the phase of developing gingivitis the percentage of coccoid cells and rods tended to decrease, while motile rods and spirochetes increased. During the 28 days of metronidazole treatment the subgingival plaque flora maintained its "healthy

  1. Metronidazole as a protector of cells from electromagnetic radiation of extremely high frequencies

    NASA Astrophysics Data System (ADS)

    Kuznetsov, Pavel E.; Malinina, Ulia A.; Popyhova, Era B.; Rogacheva, Svetlana M.; Somov, Alexander U.

    2006-08-01

    It is well known that weak electromagnetic fields of extremely high frequencies cause significant modification of the functional status of biological objects of different levels of organization. The aim of the work was to study the combinatory effect of metronidazole - the drug form of 1-(2'hydroxiethil)-2-methil-5-nitroimidazole - and electromagnetic radiation of extremely high frequencies (52...75 GHz) on the hemolytic stability of erythrocytes and hemotaxis activity of Infusoria Paramecium caudatum.

  2. Synthesis and QSAR study of novel anti-inflammatory active mesalazine-metronidazole conjugates.

    PubMed

    Naumov, Roman N; Panda, Siva S; Girgis, Adel S; George, Riham F; Farhat, Michel; Katritzky, Alan R

    2015-06-01

    Novel, mesalazine, metronidazole conjugates 6a-e with amino acid linkers were synthesized utilizing benzotriazole chemistry. Biological data acquired for all the novel bis-conjugates showed (a) some bis-conjugates exhibit comparable anti-inflammatory activity with parent drugs and (b) the potent bis-conjugates show no visible stomach lesions. 3D-pharmacophore and 2D-QSAR modeling support the observed bio-properties. PMID:25937011

  3. Effects of oral administration of metronidazole and doxycycline on olfactory capabilities of explosives detection dogs.

    PubMed

    Jenkins, Eileen K; Lee-Fowler, Tekla M; Angle, T Craig; Behrend, Ellen N; Moore, George E

    2016-08-01

    OBJECTIVE To determine effects of oral administration of metronidazole or doxycycline on olfactory function in explosives detection (ED) dogs. ANIMALS 18 ED dogs. PROCEDURES Metronidazole was administered (25 mg/kg, PO, q 12 h for 10 days); the day prior to drug administration was designated day 0. Odor detection threshold was measured with a standard scent wheel and 3 explosives (ammonium nitrate, trinitrotoluene, and smokeless powder; weight, 1 to 500 mg) on days 0, 5, and 10. Lowest repeatable weight detected was recorded as the detection threshold. There was a 10-day washout period, and doxycycline was administered (5 mg/kg, PO, q 12 h for 10 days) and the testing protocol repeated. Degradation changes in the detection threshold for dogs were assessed. RESULTS Metronidazole administration resulted in degradation of the detection threshold for 2 of 3 explosives (ammonium nitrate and trinitrotoluene). Nine of 18 dogs had a degradation of performance in response to 1 or more explosives (5 dogs had degradation on day 5 or 10 and 4 dogs had degradation on both days 5 and 10). There was no significant degradation during doxycycline administration. CONCLUSIONS AND CLINICAL RELEVANCE Degradation in the ability to detect odors of explosives during metronidazole administration at 25 mg/kg, PO, every 12 hours, indicated a potential risk for use of this drug in ED dogs. Additional studies will be needed to determine whether lower doses would have the same effect. Doxycycline administered at the tested dose appeared to be safe for use in ED dogs. PMID:27463556

  4. Clinical and Neuroradiological Spectrum of Metronidazole Induced Encephalopathy: Our Experience and the Review of Literature

    PubMed Central

    Panwar, Ajay; Pandit, Alak; Das, Susanta Kumar; Joshi, Bhushan

    2016-01-01

    Metronidazole is an antimicrobial agent mainly used in the treatment of several protozoal and anaerobic infections, additionally, is often used in hepatic encephalopathy and Crohn disease. Apart from peripheral neuropathy, metronidazole can also cause symptoms of central nervous system dysfunction like ataxic gait, dysarthria, seizures, and encephalopathy which may result from both short term and chronic use of this drug and is collectively termed as “metronidazole induced encephalopathy”(MIE). Neuroimaging forms the backbone in clinching the diagnosis of this uncommon entity, especially in cases where there is high index of suspicion of intoxication. Although typical sites of involvement include cerebellum, brain stem and corpus callosum, however, lesions of other sites have also been reported. Once diagnosed, resolution of findings on Magnetic Resonance Imaging (MRI) of the Brain along with clinical improvement remains the mainstay of monitoring. Here we review the key clinical features and MRI findings of MIE as reported in medical literature. We also analyze implication of use of this drug in special situations like hepatic encephalopathy and brain abscess and discuss our experience regarding this entity. PMID:27504340

  5. Development of Floating-Mucoadhesive Microsphere for Site Specific Release of Metronidazole

    PubMed Central

    Amin, Md. Lutful; Ahmed, Tajnin; Mannan, Md. Abdul

    2016-01-01

    Purpose: The purpose of this study was to develop and evaluate metronidazole loaded floating-mucoadhesive microsphere for sustained drug release at the gastric mucosa. Methods: Alginate gastroretentive microspheres containing metronidazole were prepared by ionic gelation method using sodium bicarbonate as gas forming agent, guar gum as mucoadhesive polymer, and Eudragit L100 as drug release modifier. Carbopol was used for increasing the bead strength. The microspheres were characterized by scanning electron microscopy and evaluated by means of drug entrapment efficiency, in vitro buoyancy, and swelling studies. In vitro mucoadhesion and drug release studies were carried out in order to evaluate site specific sustained drug release. Results: All formulations showed 100% buoyancy in vitro for a prolonged period of time. Amount of guar gum influenced the properties of different formulations. The formulation containing drug and guar gum at a ratio of 1:0.5 showed the best results with 76.3% drug entrapment efficiency, 61.21% mucoadhesion, and sustained drug release. Carbopol was found to increase surface smoothness of the microspheres. Conclusion: Metronidazole mucoadhesive-floating microspheres can be effectively used for sustained drug release to the gastric mucosa in treatment of upper GIT infection. PMID:27478781

  6. Clinical and Neuroradiological Spectrum of Metronidazole Induced Encephalopathy: Our Experience and the Review of Literature.

    PubMed

    Roy, Ujjawal; Panwar, Ajay; Pandit, Alak; Das, Susanta Kumar; Joshi, Bhushan

    2016-06-01

    Metronidazole is an antimicrobial agent mainly used in the treatment of several protozoal and anaerobic infections, additionally, is often used in hepatic encephalopathy and Crohn disease. Apart from peripheral neuropathy, metronidazole can also cause symptoms of central nervous system dysfunction like ataxic gait, dysarthria, seizures, and encephalopathy which may result from both short term and chronic use of this drug and is collectively termed as "metronidazole induced encephalopathy"(MIE). Neuroimaging forms the backbone in clinching the diagnosis of this uncommon entity, especially in cases where there is high index of suspicion of intoxication. Although typical sites of involvement include cerebellum, brain stem and corpus callosum, however, lesions of other sites have also been reported. Once diagnosed, resolution of findings on Magnetic Resonance Imaging (MRI) of the Brain along with clinical improvement remains the mainstay of monitoring. Here we review the key clinical features and MRI findings of MIE as reported in medical literature. We also analyze implication of use of this drug in special situations like hepatic encephalopathy and brain abscess and discuss our experience regarding this entity. PMID:27504340

  7. Adsorption of lysozyme on hyaluronic acid functionalized SBA-15 mesoporous silica: a possible bioadhesive depot system.

    PubMed

    Medda, Luca; Casula, Maria F; Monduzzi, Maura; Salis, Andrea

    2014-11-01

    Silica-based ordered mesoporous materials are very attractive matrices to prepare smart depot systems for several kinds of therapeutic agents. This work focuses on the well-known SBA-15 mesoporous silica and lysozyme, an antimicrobial protein. In order to improve the bioadhesion properties of SBA-15 particles, the effect of hyaluronic acid (HA) functionalization on lysozyme adsorption was investigated. SBA-15 samples having high (H-SBA) and low (L-SBA) levels of functionalization were analyzed during the three steps of the preparations: (1) introduction of the -NH2 groups to obtain the SBA-NH2 samples; (2) functionalization with HA to obtain the SBA-HA matrices; (3) adsorption of lysozyme. All silica matrices were characterized through N2-adsorption/desorption isotherms, small-angle X-ray scattering, transmission electron microscopy, thermogravimetric analysis, and Fourier transform infrared spectroscopy. The whole of the experimental data suggests that a high level of functionalization of the silica surface allows for a negligible lysozyme adsorption mainly due to unfavorable electrostatic interactions (H-SBA-NH2) or steric hindrance (H-SBA-HA). A low degree of functionalization of the silica surface brings about a very good performance toward lysozyme adsorption, being 71% (L-SBA-NH2) and 63% (L-SBA-HA) respectively, compared to that observed for original SBA-15. Finally, two different kinetic models--a "pseudo-second order" and a "intraparticle diffusion"--were compared to fit lysozyme adsorption data, the latter being more reliable than the former. PMID:25295387

  8. Preparation and characterization of a photocrosslinkable bioadhesive inspired by marine mussel.

    PubMed

    Xue, Jie; Wang, Tao; Nie, Jun; Yang, Dongzhi

    2013-02-01

    Synthetic adhesives inspired by marine mussel have attracted great attention due to its excellent water-resistance and good biocompatibility. In this study, a photocrosslinkable bioadhesive containing 3,4-Dihydroxy-l-phenylalanine (DOPA) functional group, which is central to curing mussel adhesive proteins, was prepared by ultraviolet (UV) irradiation of a new photocurable monomer ethylene glycol acrylate methacrylate-dopamine (EGAMA-DOPA) and a UV photocrosslinkable crosslinking agent poly(vinyl alcohol) (UV-PVA) derivative. The chemical structures of EGAMA-DOPA and UV-PVA were confirmed by Fourier Transform Infrared Reflection (FTIR) and (1)H NMR spectroscopy, respectively. The effects of UV light intensity, content of photoinitiator, EGAMA-DOPA and UV-PVA on the photopolymerization kinetics were studied, and the effects of the content of UV-PVA and temperature on the adhesive strength were also investigated. It was found that the higher UV light intensity, the faster polymerization rate and the higher final conversion that was the same as the trend of photoinitiator, EGAMA-DOPA and UV-PVA. And the adhesion strength measurement showed that, for gels with 30wt.% EGAMA-DOPA, the adhesion strength was obviously improved by about 150% with 3.0wt.% UV-PVA instead of pure PVA, and for gels containing 40wt.% EGAMA-DOPA, the adhesion strength sharply enhanced by 123% with increasing the content of UV-PVA from 1.0wt.% to 3.0wt.%. Cell attachment results showed good cell viability of L929 cell on the EGAMA-DOPA/UV-PVA adhesive gels. Thanks to its strong adhesion strength and good biocompatibility, such photocrosslinkable gels could be applied to the areas of biomedical field. PMID:23313836

  9. [The first metronidazole-resistant Bacteroides species isolated at Marmara University Hospital: Bacteroides thetaiotaomicron].

    PubMed

    Toprak Ülger, Nurver; Sayın, Elvan; Soyad, Ad; Dane, Faysal; Söyletir, Güner

    2013-10-01

    Bacteroides species, the predominant constituents of the human intestinal microbiota can cause serious intraabdominal and postoperative wound infections and bacteremia. Moreover, these bacteria are more resistant to antimicrobial agents than the other anaerobes. The limited number of the antimicrobials, such as carbapenems, beta-lactam/beta-lactamase inhibitors and nitroimidazoles are highly effective in eliminating Bacteroides. However, a few metronidazole-resistant isolates have been reported from several countries recently. The nim genes (nim A-G) are suggested to be responsible for the majority of the metronidazole resistance. Here, we describe a metronidazole-resistant Bacteroides thetaiotaomicron isolated from a blood culture. A gram-negative obligate anaerobic rod was isolated from the postoperative 5th day blood culture of a 62-year-old male patient with adenocarcinoma of the pancreas head. The strain was identified as B.thetaiotaomicron by using a combination of conventional tests and commercially available biochemical kits. Antimicrobial susceptibility testing was performed by agar dilution method. The resistance genes were investigated by means of PCR using specific primer pairs for nim gene. The purified PCR product was sequenced and analyzed by comparison of the consensus sequences with GenBank sequences. The MIC for metronidazole was 16 mg/L. Although the strain was intermediate according the CLSI criteria, it was resistant (> 4 mg/L) according to EUCAST criteria. The isolate was nim gene positive, and nucleotide sequencing of the PCR product shared 100% similarity with nimE gene (emb |AM042593.1 |). On the other hand the isolate was susceptible to carbapenems and sulbactam-ampicillin. Following administration of ampicillin-sulbactam, the patient's fever disappeared after 24 hours. The clinical condition improved considerably and he was discharged at day 8. The patient was followed up at the medical oncology clinic; however he died due to disease

  10. Natural Bioadhesive Biodegradable Nanoparticle-Based Topical Ophthalmic Formulations for Management of Glaucoma

    PubMed Central

    Ibrahim, Mohammed Mostafa; Abd-Elgawad, Abd-Elgawad Helmy; Soliman, Osama Abd-Elazeem; Jablonski, Monica M.

    2015-01-01

    Purpose: We prepared and characterized topical ophthalmic formulations containing brimonidine-loaded bioadhesive cationic chitosan or anionic alginate nanoparticles (NPs) for sustained release of brimonidine as once daily regimen for management of glaucoma. Methods: Nanoparticles were prepared using a spontaneous emulsification solvent diffusion method. Different concentrations of polymers, emulsifiers, and NPs stabilizers were used for formulation optimization. Nanoparticles were characterized regarding particle size, zeta potential, morphology, and drug content. Brimonidine-loaded NPs were incorporated into eye drops, a temperature-triggered in situ gelling system, and a preformed gel. They then were characterized regarding their pH, viscosity, uniformity of drug content, in vitro release characteristics, in vitro cytotoxicity, and in vivo intraocular pressure (IOP) lowering effects. Results: Characteristics of optimized brimonidine-loaded chitosan and alginate NPs, respectively, are: particle size, 115.67 ± 3.58 and 157.67 ± 5.53 nm; zeta potential, +35.27 ± 3.39 and −37.8 ± 3.77 mV; encapsulation efficiency, 74.34% ± 2.05% and 70.40% ± 2.77%; drug loading, 11.81% ± 0.67% and 13.14% ± 0.90%; and yield, 87.91% ± 5.92% and 76.53% ± 3.32%. Transmission electron microscope (TEM) analyses revealed that NPs have spherical shapes with a dense core and distinct coat. Formulations possessed uniform drug content. Furthermore, pH and viscosity were compatible with the eye. Formulations showed a sustained release without any burst effect with a Higuchi non-Fickian diffusion mechanism. Cytotoxicity studies revealed that all formulations are biocompatible. Importantly, all formulations possessed a sustained IOP lowering effect compared to the marketed brimonidine tartrate eye drops. Conclusions: These formulations provide a great improvement in topical ocular brimonidine delivery. The application of a single drop is sufficient to provide extended IOP reduction

  11. Design of novel bioadhesive materials based on mussel-derived glues

    NASA Astrophysics Data System (ADS)

    Lee, Bruce Po-Shu

    2005-11-01

    mechanical tests of DOPA-modified gels submerged in an aqueous medium demonstrated strong adhesive interaction to TiO 2, and it was confirmed that the reduced form of DOPA was responsible for the adhesion. This thesis work addressed several needs in the development of novel bioadhesive materials with improved properties in an effort to bring them closer for clinical applications.

  12. Loss of Microbiota-Mediated Colonization Resistance to Clostridium difficile Infection With Oral Vancomycin Compared With Metronidazole.

    PubMed

    Lewis, Brittany B; Buffie, Charlie G; Carter, Rebecca A; Leiner, Ingrid; Toussaint, Nora C; Miller, Liza C; Gobourne, Asia; Ling, Lilan; Pamer, Eric G

    2015-11-15

    Antibiotic administration disrupts the intestinal microbiota, increasing susceptibility to pathogens such as Clostridium difficile. Metronidazole or oral vancomycin can cure C. difficile infection, and administration of these agents to prevent C. difficile infection in high-risk patients, although not sanctioned by Infectious Disease Society of America guidelines, has been considered. The relative impacts of metronidazole and vancomycin on the intestinal microbiota and colonization resistance are unknown. We investigated the effect of brief treatment with metronidazole and/or oral vancomycin on susceptibility to C. difficile, vancomycin-resistant Enterococcus, carbapenem-resistant Klebsiella pneumoniae, and Escherichia coli infection in mice. Although metronidazole resulted in transient loss of colonization resistance, oral vancomycin markedly disrupted the microbiota, leading to prolonged loss of colonization resistance to C. difficile infection and dense colonization by vancomycin-resistant Enterococcus, K. pneumoniae, and E. coli. Our results demonstrate that vancomycin, and to a lesser extent metronidazole, are associated with marked intestinal microbiota destruction and greater risk of colonization by nosocomial pathogens. PMID:25920320

  13. DESIGN AND EVALUATION OF A METRONIDAZOLE CENTRAL CORE MATRIX TABLET

    PubMed Central

    Nagaich, Upendra; Chaudhary, Vandana; Tonpay, S.D.; Karki, Roopa

    2010-01-01

    In this paper, a study of different concentration of HPMC K 15 M exerts influence on the drug release process from a new controlled drug delivery system has been realized in order to obtain a constant release rate during a prolonged period of time, for a programmed drug release. The drug release profiles obtained for the different batches have shown an interesting relationship between the particle size of the channeling agent used and the length of different operational periods. PMID:22247836

  14. Extractional spectrophotometric analysis of metronidazole, tinidazole, ornidazole and secnidazole bases through acid-dye complexation using bromothymol blue dye.

    PubMed

    Darwish, Khaled M; Salama, Ismail; Mostafa, Samia; El-Sadek, Mohamed

    2012-01-01

    An easy, precise and valid extractional-spectrophotometric technique is described for the assessment of metronidazole (MNZ), tinidazole (TNZ), ornidazole (ONZ) and secnidazole (SNZ) in pure state and in their pharmaceutical formulations. The technique includes first the reduction of above cited drugs using HCl and zinc powder, then the formation of intense yellow colored ion-association complex species (1:3 drug/dye) using bromothymol blue (BTB) in a buffered aqueous acidic medium at pH 3-3.50. The colored products are extracted into dichloromethane and quantitatively determined at 416-420 nm. The experimental operating factors influencing the ion-pairs development were studied and optimized to obtain the maximum color intensity. The Beer plots are obeyed in the concentration ranges 2.50-22.50, 2.50-30, 7.50-35 and 5-30 μgml-1 for MNZ, TNZ, ONZ and SNZ, respectively, with correlation coefficients not less than 0.9995. The proposed technique is recommended for the routine quality control analysis of the investigated drugs in commercial tablets with no observed interference from common pharmaceutical adjuvants. Results of such analysis were statistically validated and through recovery studies, showing excellent agreement with those achieved by the reported techniques. PMID:22186332

  15. Bioadhesive sulfacetamide sodium microspheres: evaluation of their effectiveness in the treatment of bacterial keratitis caused by Staphylococcus aureus and Pseudomonas aeruginosa in a rabbit model.

    PubMed

    Sensoy, Demet; Cevher, Erdal; Sarici, Ahmet; Yilmaz, Mesut; Ozdamar, Akif; Bergişadi, Nazan

    2009-08-01

    The aim of this study was to prepare bioadhesive sulfacetamide sodium (SA) microspheres to increase their residence time on the ocular surface and to enhance their treatment efficacy on ocular keratitis. Microspheres were fabricated by spray drying method using mixture of polymers such as pectin, polycarbophil and hydroxypropylmethyl cellulose (HPMC) at different ratios. The particle size and distribution, morphological characteristics, thermal behavior, encapsulation efficiency, mucoadhesion and in vitro drug release studies on formulations have been investigated. After optimisation studies, SA-loaded polycarbophil microsphere formulation with polymer:drug ratio of 2:1 was found to be the most suitable for ocular application and used in in vivo studies. In vivo studies were carried out on New Zealand male rabbit eyes with keratitis caused by Pseudomonas aeruginosa and Staphylococcus aureus. Sterile microsphere suspension in light mineral oil was applied to infected eyes twice a day. Plain SA suspension was used as a positive control. On 3rd and 6th days of the antimicrobial therapy, the eyes were examined in respect to clinical signs of infection (blepharitis, conjunctivitis, iritis, corneal oedema and corneal infiltrates) which are the main symptoms of bacterial keratitis and then cornea samples were counted microbiologically. The rabbit eyes treated with microspheres demonstrated significantly lower clinical scores than those treated with SA alone. A significant decrease in the number of viable bacteria in eyes treated with microspheres was observed in both infection models when compared to those treated with SA alone. In conclusion, in vitro and in vivo studies showed that SA-loaded microspheres were proven to be highly effective in the treatment of ocular keratitis. PMID:19223014

  16. Structure of RdxA: an oxygen insensitive nitroreductase essential for metronidazole activation in Helicobacter pylori

    PubMed Central

    Martínez-Júlvez, Marta; Rojas, Adriana L.; Olekhnovich, Igor; Angarica, Vladimir Espinosa; Hoffman, Paul S.; Sancho, Javier

    2012-01-01

    The RdxA oxygen insensitive nitroreductase of the human gastric pathogen Helicobacter pylori is responsible for the susceptibility of this organism to the redox active prodrug metronidazole (MTZ). Loss-of-function mutations in rdxA are primarily responsible for resistance to this therapeutic. RdxA exhibits potent NADPH oxidase activity under aerobic conditions and metronidazole reductase activity under strictly anaerobic conditions. Here we report the crystal structure of RdxA, which is a homodimer exhibiting domain swapping and containing two molecules of FMN bound at the dimer interface. We have found a gap between the side chain of Tyr47 and the isoalloxazine ring of FMN that seems appropriate for substrate binding. The structure does not include residues 97–128, which corresponds to a locally unstable part of the NTR from E. coli, and might be involved in cofactor binding. Comparison of H pylori RdxA to other oxidoreductases of known structure suggests RdxA may belong to a new subgroup of oxidoreductases in which a cysteine sidechain close to the FMN cofactor could be involved in the reductive activity. In this respect, mutation of C159 to A or S (C159A/S) has resulted in loss of MTZ reductase activity, but not NADPH oxidase activity. The RdxA structure allows interpretation of the many loss-of-function mutations previously described, including those affecting C159, a residue whose interaction with FMN is required for nitroreduction of MTZ. Our studies provide unique insights into the redox behavior of the flavin in this key enzyme for metronidazole activation, and with potential use in gene therapy. PMID:23039228

  17. Influence of metronidazole particle properties on granules prepared in a high-shear mixer-granulator.

    PubMed

    Di Martino, Piera; Censi, Roberta; Malaj, Ledjan; Martelli, Sante; Joiris, Etienne; Barthélémy, Christine

    2007-02-01

    Metronidazole is a good example of high-dose drug substance with poor granulating and tableting properties. Tablets are generally produced by liquid granulation; however, the technological process failure is quite frequent. In order to verify how the metronidazole particle characteristics can influence granule properties, three metronidazole batches differing for crystal habit, mean particle size, BET surface area and wettability were selected, primarily designed according to their different elongation ratio: needle-shaped, stick-shaped, and isodimensional. In the presence of lactose monohydrate and pregelatinized maize starch, respectively as diluent and binder, they were included in a formula for wet granulation in a high-shear mixer-granulator. In order to render the process comparable as far as possible, all parameters and experimental conditions were maintained constant. Four granule batches were obtained: granules from placebo (G-placebo), granules from needle-shaped crystals (G-needle-shaped), granules from stick-shaped crystals (G-stick-shaped), and granules from isodimensional crystals (G-isodimensional). Different granule properties were considered, in particular concerning porosity, friability, loss on drying (LOD), and flowability. In order to study their tabletability and compressibility, the different granules obtained were then compressed in a rotary press. The best tabletability was obtained with the isodimensional batch, while the poorest was exhibited by the stick-shaped one. Differences in tabletability are in good accordance with compressibility results: to a better tabletability corresponds an important granule ability to undergo a volume reduction as a result of an applied pressure. In particular, it was proposed that the greatest compressibility of the G-isodimensional must be related to the greatest granule porosity percentage. PMID:17454043

  18. Cytotoxicity of metronidazole (Flagyl) and misonidazole (Ro-07-0582): enhancement by lactate.

    PubMed Central

    Mahood, J. S.; Willson, R. L.

    1981-01-01

    The cytotoxic activity of metronidazole (Flagyl) and misonidazole (MISO) to hypoxic Chinese hamster ovary (CHO) cells suspended in standard medium in sealed vials and in gassed spinner flasks has been investigated. Flagyl (5 mM) was only cytotoxic at high initial cell densities. However, when lactate (20 mM) was included in the medium the cytotoxicity of Flagyl at low cell densities was considerable, and similar to that of misonidazole under the same conditions. The relevance of this "lactate effect" to in vivo systems, and the possible mechanisms involved, are discussed. PMID:7225286

  19. Pharmacokinetics of metronidazole in foals: influence of age within the neonatal period.

    PubMed

    Swain, E A; Magdesian, K G; Kass, P H; Edman, J E; Knych, H K

    2015-06-01

    Neonatal foals have unique pharmacokinetics, which may lead to accumulation of certain drugs when adult horse dosage regimens are used. Given its lipophilic nature and requirement for hepatic metabolism, metronidazole may be one of these drugs. The purpose of this study was to determine the pharmacokinetic profiles of metronidazole in twelve healthy foals at 1-2.5 days of age when administered as a single intravenous (IV) and intragastric (IG) dose of 15 mg/kg. Foals in the intravenous group were studied a second time at 10-12 days of age to evaluate the influence of age on pharmacokinetics within the neonatal period. Blood samples were collected at serial time points after metronidazole administration. Metronidazole concentration in plasma was measured using LC-MS. Pharmacokinetic parameters were determined using noncompartmental analysis and compared between age groups. At 1-2.5 days of age, the mean peak plasma concentration after IV infusion was 18.79 ± 1.46 μg/mL, elimination half-life was 11.8 ± 1.77 h, clearance was 0.84 ± 0.13 mL/min/kg and the volume of distribution (steady-state) was 0.87 ± 0.07 L/kg. At 10-12 days of age, the mean peak plasma concentration after IV infusion was 18.17 ± 1.42 μg/mL, elimination half-life was 9.07 ± 2.84 h, clearance was 1.14 ± 0.21 mL/min/kg and the volume of distribution (steady-state) was 0.88 ± 0.06 L/kg. Oral approximated bioavailability was 100%. Cmax and Tmax after oral dosing were 14.85 ± 0.54 μg/mL and 1.75 (1-4) h, respectively. The elimination half-life was longer and clearance was reduced in neonatal foals at 1-2.5 days as compared to 10-12 days of age (P = 0.006, P = 0.001, respectively). This study warrants consideration for altered dosing recommendations in foals, especially a longer interval (12 h). PMID:25271172

  20. Double-blind test of metronidazole and tinidazole in the treatment of asymptomatic Entamoeba histolytica and Entamoeba hartmanni carriers.

    PubMed

    Spillmann, R; Ayala, S C; Sanchez, C E

    1976-07-01

    One hundred and fifteen persons with asymptomatic Entamoeba histolytica or E. hartmanni infection, or both, were given metronidazole (750 mg three times daily for 5 days), tinidazole (1 g twice daily on 2 consecutive days), or a starch placebo. Three post-treatment stools were examined in the 2 weeks following initiation of treatment. Cysts of E. histolytica reappeared in the stools of 37% of 30 given metronidazole, 62% of 34 given tinidazole, and 70% of 31 given placebo. Cysts of E. hartmanni reappeared in the stools of 46% of 24 given metronidazole, 69% of 16 given tinidazole, and 90% of 10 given placebo. Rapid absorption and short duration of treatment make both drugs ineffective for the treatment of ameba carriers. PMID:183554

  1. Kinetic and mechanistic studies of the photolysis of metronidazole in simulated aqueous environmental matrices using a mass spectrometric approach.

    PubMed

    Tong, Lei; Pérez, Sandra; Gonçalves, Carlos; Alpendurada, Fátima; Wang, Yanxin; Barceló, Damià

    2011-01-01

    Metronidazole is a nitroimidazole antibiotic derivative used in humans against anaerobic bacteria and protozoa. In light of the recent detection of metronidazole in hospital wastes, sewage treatment plants, and surface waters, along with its known sensitivity toward photolytical degradation, this study aimed to model the photolysis in environmental waters by sunlight as a natural attenuation process. To this end, the degradation of metronidazole in a photoreactor simulating solar radiation (Suntest CPS) was compared in five different aqueous matrices: deionized water, artificial freshwater (AFW), AFW supplemented with nitrate (5 mg/L), AFW containing humic acids, and AFW with both nitrate and humic acids. Irrespective of the test medium, the degradation of the metronidazole solutions (10 and 0.02 mg/L) was found to follow pseudo-first-order kinetics. Degradation rates were dependant on the matrix, with humic acids causing a two to threefold decrease in the rate constants while the presence of nitrate had no marked effect on the kinetics. Therefore, the direct photolysis of metronidazole was apparently attenuated through a filter effect of humic acids. Screening of the irradiated water samples by ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry allowed separation and characterisation of four principal phototransformation products of the antibiotic. The high-resolution MS data pointed to the formation of two rearrangement products (C(6)H(10)N(3)O(3)) isobaric with metronidazole, a third product deriving from the elimination of NO from the nitro group (C(6)H(11)N(2)O(2)), and a fourth unidentified degradate with a likely elemental composition of C(5)H(10)N(3)O. PMID:20978747

  2. [Comparative study for the evaluation of the efficacy and safety of metronidazole and secnidazole in the treatment of vaginal trichomoniasis].

    PubMed

    Buitrón García Figueroa, R; Gonzalo Butrón López, F; Oropez Rechy, G; Romero-Cabello, R

    1997-11-01

    Presently study included 3 groups of 20 women with tricomoniasis demonstrated parasitologicaly for oozing vaginal, the first group received treatment with vaginal ova with metronidazol for 10 days, the second group ova of secnidazol for 3 days and the third group ova of secnidazol for 7 days. The results showed that the clinical manifestations dimanished significantly and the presence of Trichomonas vaginalis disappeared from the vaginal cavity, therefore cure was achieved parasitological in all the cases. We concluded that they are equally useful the metronidazol for 10 days, and the secnidazol for 3 or 7 days, without the presence of adverse effects. PMID:9441152

  3. Over 20% (15)N Hyperpolarization in Under One Minute for Metronidazole, an Antibiotic and Hypoxia Probe.

    PubMed

    Barskiy, Danila A; Shchepin, Roman V; Coffey, Aaron M; Theis, Thomas; Warren, Warren S; Goodson, Boyd M; Chekmenev, Eduard Y

    2016-07-01

    Direct NMR hyperpolarization of naturally abundant (15)N sites in metronidazole is demonstrated using SABRE-SHEATH (Signal Amplification by Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei). In only a few tens of seconds, nuclear spin polarization P(15)N of up to ∼24% is achieved using parahydrogen with 80% para fraction corresponding to P(15)N ≈ 32% if ∼100% parahydrogen were employed (which would translate to a signal enhancement of ∼0.1-million-fold at 9.4 T). In addition to this demonstration on the directly binding (15)N site (using J(2)H-(15)N), we also hyperpolarized more distant (15)N sites in metronidazole using longer-range spin-spin couplings (J(4)H-(15)N and J(5)H-(15)N). Taken together, these results significantly expand the range of molecular structures and sites amenable to hyperpolarization via low-cost parahydrogen-based methods. In particular, hyperpolarized nitroimidazole and its derivatives have powerful potential applications such as direct in vivo imaging of mechanisms of action or hypoxia sensing. PMID:27321159

  4. SUSCEPTIBILITY OF STRICT AND FACULTATIVE ANAEROBES ISOLATED FROM ENDODONTIC INFECTIONS TO METRONIDAZOLE AND β-LACTAMS

    PubMed Central

    Gaetti-Jardim, Elerson; Landucci, Luís Fernando; Lins, Samira Âmbar; Vieira, Evanice Menezes Marçal; de Oliveira, Sérgio Ricardo

    2007-01-01

    Endodontic infections are mixed aerobic-anaerobic infections and several microbial groups associated to these pathologies are also involved in orofacial infections. The goal of this study was to evaluate the susceptibility of microorganisms isolated from endodontic infections to β-lactams and metronidazole and verify the production of β-lactamases. Clinical specimens were collected from 58 endodontic infections of 52 patients. The microorganisms were isolated in selective and non-selective culture media, under anaerobiosis and aerobiosis, and identified using biochemical methods. In the susceptibility tests, it was used an agar dilution method, and Wilkins-Chalgren agar enriched with blood, hemin and menadione for the anaerobes, while Mueller- Hinton agar was employed for the facultative anaerobes. The production of β-lactamases was evaluated through the biological and chromogenic cephalosporin methods. All tested isolates were sensitive to imipenem and 99.3% to amoxicillin/clavulanate association, while 16.1% showed resistance to amoxicillin and penicillin G, and 4.89% to cefoxitin. Resistance to metronidazole was just found in facultative anaerobes. Production of β-lactamases was detected in 18.2% of the isolates and presented a correlation with resistance to β-lactams. PMID:19089195

  5. The role of several l-HPCs in preventing tablet capping during direct compression of metronidazole.

    PubMed

    Martino, Piera Di; Malaj, Ledjan; Censi, Roberta; Martelli, Sante; Joiris, Etienne; Barthélémy, Christine

    2007-12-01

    Several low-hydroxypropyl cellulose (l-HPC) derivatives (LH-11, 21, 22, 31, and 32) differing in granulometric particle size or in hydroxypropyl content were considered in the present study. The l-HPC grades were characterized as pure powders, in order to determine both compression and densification behavior, in presence or in absence of magnesium stearate as lubricant, and then, were physically mixed in different proportions with metronidazole, which was also previously characterized as pure powder. The tabletability and compressibility of these binary mixtures were then evaluated, in presence or in absence magnesium stearate as lubricant at two different compression speeds (20 and 70 mm/sec). It was observed that both binary mixture compression behavior and capping tendency were influenced by compression speed and by the presence of lubricant. Differences in anti-capping efficiency between the l-HPCs may be related to their hydroxypropyl content. This parameter influences the interaction between the metronidazole and the polymer particles, and consequently the ability of the binary system to undergo densification under compression. PMID:18097804

  6. Metronidazole Injection

    MedlinePlus

    ... care provider may tell you to stop your infusion if you have a mechanical problem (such as ... or catheter); if you have to stop an infusion, call your health care provider immediately so your ...

  7. Metronidazole Injection

    MedlinePlus

    ... effectiveness and side effects of your treatment using laboratory tests and physical examinations. It is important to keep all appointments with your doctor and the laboratory. The length of treatment depends on how your ...

  8. Metronidazole Topical

    MedlinePlus

    ... instructions provided with it and follow these steps: Fill the special applicator that comes with the gel to the level indicated. Lie on your back with your knees drawn upward and spread apart. ...

  9. Detection of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans after Systemic Administration of Amoxicillin Plus Metronidazole as an Adjunct to Non-surgical Periodontal Therapy: A Systematic Review and Meta-Analysis

    PubMed Central

    Dakic, Aleksandar; Boillot, Adrien; Colliot, Cyrille; Carra, Maria-Clotilde; Czernichow, Sébastien; Bouchard, Philippe

    2016-01-01

    Objective: To evaluate the variations in the detection of Porphyromonas gingivalis and/or Aggregatibacter actinomycetemcomitans before and after systemic administration of amoxicillin plus metronidazole in association with non-surgical periodontal therapy (NSPT). Background: The adjunctive use of antibiotics has been advocated to improve the clinical outcomes of NSPT. However, no systematic review has investigated the microbiological benefit of this combination. Materials and Methods: An electronic search was conducted up to December 2015. Randomized clinical trials comparing the number of patients testing positive for P. gingivalis and/or A. actinomycetemcomitans before and after NSPT with (test group) or without (control group) amoxicillin plus metronidazole were included. The difference between groups in the variation of positive patients was calculated using the inverse variance method with a random effects model. Results: The frequency of patients positive for A. actinomycetemcomitans was decreased by 30% (p = 0.002) and by 25% (p = 0.01) in the test group compared to the control group at 3- and 6-month follow-up, respectively. Similar findings were observed when considering the frequency of patients positive for Porphyromonas gingivalis, with a reduction by 28% (p < 0.0001), 32% (p < 0.0001), and 34% (p = 0.03) in the test group compared to the control group at 3-, 6-, and 12-month follow-up, respectively. Conclusion: The systemic administration of amoxicillin plus metronidazole as an adjunct to NSPT significantly decreased the number of patients positive for P. gingivalis and A. actinomycetemcomitans compared with periodontal therapy alone or with a placebo. PMID:27594851

  10. Development of an ex vivo retention model simulating bioadhesion in the oral cavity using human saliva and physiologically relevant irrigation media.

    PubMed

    Madsen, Katrine D; Sander, Camilla; Baldursdottir, Stefania; Pedersen, Anne Marie L; Jacobsen, Jette

    2013-05-20

    In recent years, there has been a particular interest in bioadhesive formulations for oromucosal drug delivery as this may promote prolonged local therapy and enhanced systemic effect. Saliva plays a vital role in oromucosal drug absorption by dissolving the drug and presenting it to the mucosal surface. However, the rheological, chemical, and interfacial properties of this complex biological fluid may strongly affect the adhesion of bioadhesive formulations. There is a need for well characterized in vitro models to assess the bioadhesive properties of oral dosage forms for administration in the oral cavity. Thus we aimed at developing an advanced ex vivo buccal retention model, with focus on choosing a physiologically relevant irrigation media closely resembling human saliva. Spray dried chitosan microparticles containing metformin hydrochloride as an example of a small hydrophilic drug, were employed as bioadhesive formulations. Chewing-stimulated human whole saliva was collected and characterized for use in retention studies in comparison with four artificial irrigation media; phosphate buffer, Saliva Orthana(®), porcine gastric mucin base media (PGM3), and xanthan gum based media (XG2). Retention of metformin, applied as spray dried microparticles on porcine buccal mucosa, greatly depended on the characteristics of the irrigation media. When rheology of the irrigation media was examined, changes in retention profiles could be interpreted, as irrigation media containing mucin and xanthan gum possessed a higher viscosity than phosphate buffer, which led to longer retention of the drug due to better hydration of the mucosa and the spray dried microparticles. Metformin retention profiles were comparable when human saliva, Saliva Orthana(®), or PGM3 were used as irrigation media. Moreover, PGM3 displayed physico-chemical properties closest to those of human saliva with regard to pH, protein content and surface tension. Saliva Orthana(®) and PGM3 are therefore

  11. [Determination of common antibiotics and metronidazole in cosmetics by ultra performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Liu, Hualiang; Li, Fang; Yang, Run; Wang, Lianhong; Ma, Yongji

    2009-01-01

    A method for the analysis of common antibiotics and metronidazole in cosmetics was developed by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/ MS). One gram of each cosmetic sample was extracted by methanol-water containing 0.1 mol/L formic acid (1:1, v/v). The extracted sample was filtered before being analyzed with UPLC/MS/MS. The effects of formic acid concentration in the mobile phase on the sensitivity and retention time were studied, and the results showed that 1% was the optimum concentration. Seven analytes, minocycline, oxytetracycline, tetracycline, chlortetracycline, doxycycline, chloramphenicol, metronidazole, can be separated and detected in 5 min, which is much faster than that by the conventional liquid chromatography. The detection limits were 3 - 20 ng/g, and the recoveries were 87% -101%. The calibration curves showed good linearity in the range of 2 - 1 000 microg/L with correlation coefficients larger than 0.995. The method was also applied to determine common antibiotics and metronidazole in 11 real samples from the market. Chloramphenicol was detected in 2 samples and the concentrations were 0.37% and 0.19%; metronidazole was detected in 1 sample and the concentration was 1.02%; others were not detected. PMID:19449540

  12. High rate of non-susceptibility to metronidazole and clindamycin in anaerobic isolates: Data from a clinical laboratory from Karachi, Pakistan.

    PubMed

    Sheikh, Sadia Omer; Jabeen, Kauser; Qaiser, Saba; Ahsan, Syed Tanwir; Khan, Erum; Zafar, Afia

    2015-06-01

    Due to increasing resistance amongst anaerobic pathogens periodic surveillance of resistance has been recommended in regional/local settings. Anaerobic antimicrobial susceptibility testing is not routinely performed in many laboratories in Pakistan, hence absence of local data may lead to inappropriate empirical therapy in serious cases. 121 clinically significant anaerobic strains (26/121; 21% bacteremic isolates) were isolated and saved from 2010 to 2011. Susceptibility testing against metronidazole, clindamycin, co-amoxiclav, meropenem, piperacillin/tazobactam, linezolid and gatifloxacin was performed by determining minimum inhibitory concentrations (MICs). A high proportion of non-susceptible strains to metronidazole (10% of 121 isolates) and clindamycin (12% of 121 isolates) was seen, most noticeable in Bacteroides fragilis. Three Bacteroides species strains were non-susceptible to both metronidazole and clindamycin. One strain of Clostridium species was fully resistant to metronidazole and had intermediate resistance to clindamycin. No resistance to any of the other tested antibiotics was seen. Resistance to metronidazole was higher in bacteremic vs. non bacteremic isolates (p = value 0.07). In our setting where there is a high usage of empirical metronidazole and clindamycin for the treatment of serious anaerobic infections clinicians should be aware of increased resistance to these agents. Periodic surveillance of resistance to anti-anaerobic drugs especially metronidazole and clindamycin should be performed to generate antibiogram and guide appropriate empiric therapy. PMID:25800668

  13. The redox-active drug metronidazole and thiol-depleting garlic compounds act synergistically in the protist parasite Spironucleus vortens.

    PubMed

    Williams, C F; Vacca, A R; Dunham, L; Lloyd, D; Coogan, M P; Evans, G; Graz, M; Cable, J

    2016-01-01

    Spironucleus vortens is a protozoan parasite associated with significant mortalities in the freshwater angelfish, Pterophyllum scalare. Control of this parasite is especially problematic due to restrictions on the use of the drug of choice, metronidazole (MTZ), on fish farms. Use of garlic (Allium sativum) is undergoing a renaissance following experimental validations of its antimicrobial efficiency. Ajoene ((E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide), is a stable transformation product of allicin, the primary biologically active component of garlic. In the current study, an ajoene oil crude extract had a minimum inhibitory concentration (MIC) of 40μg/ml against S. vortens. GC-MS and NMR spectroscopy revealed this ajoene extract contained a mixture of the (E) and (Z)-ajoene isomers along with diallyl disulphide (DADS) and diallyl trisulphide (DATS). The only component of the ajoene crude oil found to substantially inhibit S. vortens growth by optical density monitoring (Bioscreen C Reader) was (Z)-ajoene (MIC 16μg/ml). Ajoene oil acted in synergy with MTZ in vitro, reducing the individual MIC of this drug (4μg/ml) by 16-fold, and that of ajoene oil by 200-fold with a fractional inhibitory concentration (FIC) index of 0.263. This synergistic interaction was confirmed in vivo. S. vortens-infected Pterophyllum scalare angelfish dosed orally with 0.5% (v/w) MTZ combined with 0.05% (v/w) ajoene displayed a significant reduction in faecal trophozoite count, whilst those fed on 0.5% MTZ flakes (half the recommended oral dose) alone did not. This study demonstrates for the first time the synergistic interaction between the synthetic drug MTZ and natural ajoene oil both in vitro and in vivo. Future work should evaluate the potential synergy of ajoene and MTZ against MTZ-resistant bacteria and protists. PMID:26968264

  14. Evaluation of Giardia duodenalis viability after metronidazole treatment by flow cytometry

    PubMed Central

    Barbosa, Joana; Rodrigues, Acácio Gonçalves; Pérez, Maria José; Pina-Vaz, Cidália

    2014-01-01

    Giardia duodenalis (syn. lamblia; syn. intestinalis) susceptibility testing is not routinely performed because the classical culture methods are very time-consuming and laborious. We developed a novel flow cytometry (FC) assay to evaluate the susceptibility of G. duodenalis trophozoites to metronidazole (MTZ). Different concentrations of MTZ were added to cultures of trophozoites (10 5 /mL) and the cultures were incubated for different periods. The 50% inhibitory concentration was calculated and propidium iodide (PI) was used to quantify the number of dead cells. After treatment, PI-positive trophozoites increased with increasing drug concentration and exposure time. An excellent correlation was found between FC and the classical method. A novel, accurate and reliable method is now available to evaluate G. duodenalis viability. PMID:25424449

  15. Effect of ionic crosslink on the release of metronidazole from partially carboxymethylated guar gum tablet.

    PubMed

    Singh, Rakesh; Maity, Siddhartha; Sa, Biswanath

    2014-06-15

    Partially carboxymethylated guar gum (PCMGG) was crosslinked in situ by Ca(2+) ions during wet massing step of tablet preparation. The resulting tablets were evaluated for the effect of the extent of crosslinking on drug release and matrix swelling. Increase in the concentration of Ca(2+) ions increased the viscosity of gel layer and reduced the water penetration velocity into the matrix with subsequent decrease in swelling of the tablets and drug release. Beyond a certain concentration of Ca(2+) ions, the viscosity of the gel layer decreased and the drug release rate increased primarily due to erosion of the matrix. The mechanism of drug release appeared to be non-Fickian or anomalous transport. The release data also best fitted in zero order equation. The model drug, metronidazole, was compatible with the matrix materials as evident from instrumental analyses. Such formulation may provide flexibility in achieving the desired drug release rate from crosslinked matrix tablets. PMID:24721097

  16. Granular Formation during Apoptosis in Blastocystis sp. Exposed to Metronidazole (MTZ)

    PubMed Central

    Suresh, Kumar; Tan, Tian Chye

    2016-01-01

    The role and function of the granular life cycle stage in Blastocystis sp, remains uncertain despite suggestions being made that the granules are metabolic, reproductive and lipid in nature. This present study aims to understand granular formation by triggering apoptosis in Blastocystis sp. by treating them with metronidazole (MTZ). Blastocystis sp.cultures of 4 sub-types namely 1, 2, 3 and 5 when treated with 0.01 and 0.0001 mg/ml of metronidazole (MTZ) respectively showed many of the parasites to be both viable and apoptotic (VA). Treated subtype 3 isolates exhibited the highest number of granular forms i.e. 88% (p<0.001) (0.0001 mg/ml) and 69% (p<0.01) (0.01 mg/ml) respectively at the 72 h in in vitro culture compared to other subtypes. These VA forms showed distinct granules using acridine orange (AO) and 4’,6-diamino-2-phenylindole (DAPI) staining with a mean per cell ranging from 5 in ST 5 to as high as 16 in ST 3. These forms showed intact mitochondria in both viable apoptotic (VA) and viable non-apoptotic (VNA) cells with a pattern of accumulation of lipid droplets corresponding to viable cells. Granular VA forms looked ultra-structurally different with prominent presence of mitochondria-like organelle (MLO) and a changed mitochondrial trans-membrane potential with thicker membrane and a highly convoluted inner membrane than the less dense non-viable apoptotic (NVA) cells. This suggests that granular formation during apoptosis is a self-regulatory mechanism to produce higher number of viable cells in response to treatment. This study directs the need to search novel chemotherapeutic approaches by incorporating these findings when developing drugs against the emerging Blastocystis sp. infections. PMID:27471855

  17. Granular Formation during Apoptosis in Blastocystis sp. Exposed to Metronidazole (MTZ).

    PubMed

    Dhurga, Devi Balkrishnan; Suresh, Kumar; Tan, Tian Chye

    2016-01-01

    The role and function of the granular life cycle stage in Blastocystis sp, remains uncertain despite suggestions being made that the granules are metabolic, reproductive and lipid in nature. This present study aims to understand granular formation by triggering apoptosis in Blastocystis sp. by treating them with metronidazole (MTZ). Blastocystis sp.cultures of 4 sub-types namely 1, 2, 3 and 5 when treated with 0.01 and 0.0001 mg/ml of metronidazole (MTZ) respectively showed many of the parasites to be both viable and apoptotic (VA). Treated subtype 3 isolates exhibited the highest number of granular forms i.e. 88% (p<0.001) (0.0001 mg/ml) and 69% (p<0.01) (0.01 mg/ml) respectively at the 72 h in in vitro culture compared to other subtypes. These VA forms showed distinct granules using acridine orange (AO) and 4',6-diamino-2-phenylindole (DAPI) staining with a mean per cell ranging from 5 in ST 5 to as high as 16 in ST 3. These forms showed intact mitochondria in both viable apoptotic (VA) and viable non-apoptotic (VNA) cells with a pattern of accumulation of lipid droplets corresponding to viable cells. Granular VA forms looked ultra-structurally different with prominent presence of mitochondria-like organelle (MLO) and a changed mitochondrial trans-membrane potential with thicker membrane and a highly convoluted inner membrane than the less dense non-viable apoptotic (NVA) cells. This suggests that granular formation during apoptosis is a self-regulatory mechanism to produce higher number of viable cells in response to treatment. This study directs the need to search novel chemotherapeutic approaches by incorporating these findings when developing drugs against the emerging Blastocystis sp. infections. PMID:27471855

  18. Influence of Hydroxypropyl Methylcellulose on Metronidazole Crystallinity in Spray-Congealed Polyethylene Glycol Microparticles and Its Impact with Various Additives on Metronidazole Release.

    PubMed

    Oh, Ching Mien; Heng, Paul Wan Sia; Chan, Lai Wah

    2015-12-01

    The purpose of this study was to investigate the effect of a hydrophilic polymer, hydroxypropyl methylcellulose (HPMC), on the crystallinity and drug release of metronidazole (MNZ) in spray-congealed polyethylene glycol (PEG) microparticles and to further modify the drug release using other additives in the formulation. HPMC has been used in many pharmaceutical formulations and processes but to date, it has not been employed as an additive in spray congealing. Crystallinity of a drug is especially important to the development of pharmaceutical products as active pharmaceutical ingredients (APIs) are mostly crystalline in nature. A combination of X-ray diffractometry, differential scanning calorimetry, Raman spectroscopy and Fourier transform-infrared spectroscopy (FT-IR) spectroscopy was employed to investigate the degree of crystallinity and possible solid-state structure of MNZ in the microparticles. The microparticles with HPMC were generally spherical. Spray congealing decreased MNZ crystallinity, and the presence of HPMC reduced the drug crystallinity further. The reduction in MNZ crystallinity was dependent on the concentration of HPMC. Smaller HPMC particles also resulted in a greater percentage reduction in MNZ crystallinity. Appreciable modification to MNZ release could be obtained with HPMC. However, this was largely attributed to the role of HPMC in forming a diffusion barrier. Further modification of drug release from spray-congealed PEG-HPMC microparticles was achieved with the addition of 5% w/w dicalcium phosphate but not with magnesium stearate, methyl cellulose, polyvinylpyrrolidone, silicon dioxide and sodium oleate/citric acid. Dicalcium phosphate facilitated formation of the diffusion barrier. PMID:25933626

  19. Recombinant mussel adhesive protein fp-5 (MAP fp-5) as a bulk bioadhesive and surface coating material.

    PubMed

    Choi, Yoo Seong; Kang, Dong Gyun; Lim, Seonghye; Yang, Yun Jung; Kim, Chang Sup; Cha, Hyung Joon

    2011-08-01

    Mussel adhesive proteins (MAPs) attach to all types of inorganic and organic surfaces, even in wet environments. MAP of type 5 (fp-5), in particular, has been considered as a key adhesive material. However, the low availability of fp-5 has hampered its biochemical characterization and practical applications. Here, soluble recombinant fp-5 is mass-produced in Escherichia coli. Tyrosinase-modified recombinant fp-5 showed ∼1.11 MPa adhesive shear strength, which is the first report of a bulk-scale adhesive force measurement for purified recombinant of natural MAP type. Surface coatings were also performed through simple dip-coating of various objects. In addition, complex coacervate using recombinant fp-5 and hyaluronic acid was prepared as an efficient adhesive formulation, which greatly improved the bulk adhesive strength. Collectively, it is expected that this work will enhance basic understanding of mussel adhesion and that recombinant fp-5 can be successfully used as a realistic bulk-scale bioadhesive and an efficient surface coating material. PMID:21770718

  20. Interfacial Cohesion and Assembly of Bioadhesive Molecules for Design of Long-Term Stable Hydrophobic Nanodrugs toward Effective Anticancer Therapy.

    PubMed

    Shen, Guizhi; Xing, Ruirui; Zhang, Ning; Chen, Chengjun; Ma, Guanghui; Yan, Xuehai

    2016-06-28

    The majority of anticancer drugs are poorly water-soluble and thus suffer from rather low bioavailability. Although a variety of delivery carriers have been developed for bioavailability improvement, they are severely limited by low drug loading and undesired side effects. The optimum delivery vehicle would be a biocompatible and biodegradable drug nanoparticle of uniform size with a thin but stable shell, making it soluble, preventing aggregation and enabling targeting. Here, we present a general strategy for the rational design of hydrophobic drug nanoparticles with high drug loading by means of interfacial cohesion and supramolecular assembly of bioadhesive species. We demonstrate that the pathway is capable of effectively suppressing and retarding Ostwald ripening, providing drug nanoparticles with small and uniform size and long-term colloidal stability. The final complex drug nanoparticles provide higher tumor accumulation, negligible toxicity, and enhanced antitumor activity, superior to commercial formulations. Our findings demonstrate that local, on-demand coating of hydrophobic nanoparticles is achievable through cooperation and compromise of interfacial adhesion and assembly. PMID:27223166

  1. Application of Ulex europaeus agglutinin I-modified liposomes for oral vaccine: Ex Vivo bioadhesion and in Vivo immunity.

    PubMed

    Li, KeXin; Zhao, Xiuli; Xu, Shiyi; Pang, DaHai; Yang, ChunRong; Chen, DaWei

    2011-01-01

    The conjugation of Ulex europaeus agglutinin I (UEAI) onto surface of liposomes has been demonstrated to effectively improve the intestinal absorption of antigen, subsequently induced strong mucosal and systemic immune responses. In this context, we prepared bovine serum albumin (BSA)-encapsulating UEAI-modified liposomes (UEAI-LIP) and unmodified ones (LIP). The specific bioadhesion on mice gastro-intestinal mucosa was studied ex vivo. An important increase of interaction between UEAI-conjugated liposomes and the intestinal segments with Peyer's Patches (PPs) was observed compared with the unconjugated one (p<0.01). However, under the presence of α-L-fucose, which is the reported specific sugar for UEAI, specifically inhibited the activity of these conjugates. The immune-stimulating activity in vivo was studied by measuring immunoglobulin G (IgG) levels in serum and immunoglobulin A (IgA) levels in intestinal mucosal secretions following oral administration of BSA solution, LIP and UEAI-LIP in mice. Results indicate that antigen encapsulated in liposomes, especially the UEAI-modified ones, was favorable for inducing immune response. At 42 d after the first immunization, the highest IgG and IgA antibody levels produced by UEAI-LIP occurred, respectively showing 4.4-fold and 5-fold higher levels compared to those of the groups receiving BSA alone. This data demonstrated high potential of UEAI-modified liposomes for their use as carrier for oral vaccines. PMID:21532200

  2. Comparison of the Effects of Myrtus Communis L, Berberis Vulgaris and Metronidazole Vaginal Gel alone for the Treatment of Bacterial Vaginosis

    PubMed Central

    Masoudi, Mansoureh; Rafieian-Kopaei, Mahmoud

    2016-01-01

    Introduction There is a growing tendency towards herbal medicines for treatment of vaginitis. Antibacterial and antifungal effects of Myrtus communis L and Berberis vulgaris have been demonstrated invitro and invivo. Aim This study aimed to compare the therapeutic effects of the vaginal gel of Berberis vulgaris 5% (in metronidazole base) and Myrtus communis L 2% (in metronidazole base) with only metronidazole vaginal gel 0.75% on bacterial vaginosis. Materials and Methods This study was a randomized clinical trial research on 120 married women aged 18-40 years affected by bacterial vaginosis attended for treatment to gynaecology clinic of Hajar Hospital (Shahrekord, Iran). They were randomly divided into three groups of 40 participants. Diagnostic criteria were Amsel’s criteria. Myrtus communis L, Berberis vulgaris vaginal gel or metronidazole vaginal gel for five-night usage were prescribed to each group, and after 7 days therapeutic effects were assessed. Data analysis was performed using ANOVA and Chi-square tests. Results A statistically significant difference was observed with regard to treatment response among the study groups (p<0.001), with Myrtus communis L and Berberis vulgaris groups having a better response than metronidazole gel alone. Moreover, there was no significant difference between Myrtus communis L and Berberis vulgaris groups (p= 0.18). The patients in groups of Myrtus communis L or Berberis vulgaris in metronidazole base did not experience any relapse, but in metronidazole group, 30% of patients experienced relapse during three weeks follow up. Conclusion Findings of the study showed that treatment with a combination of Myrtus communis L or Berberis vulgaris in metronidazole base improve the efficacy of bacterial vaginosis therapy. PMID:27134945

  3. [Clinical Characteristics of Metronidazole-induced Encephalopathy: A Report of Two Cases and a Review of 32 Japanese Cases in the Literature].

    PubMed

    Kato, Hideaki; Sosa, Hiroko; Mori, Masaaki; Kaneko, Takeshi

    2015-09-01

    Metronidazole is an antibiotic classically used against most anaerobic bacteria and protozoa. Because an intravenous form of metronidazole has recently entered the market, the use of this antibiotic is attracting renewed interest in many clinical settings in Japan. However, neurotoxicity is a major adverse event: in the central nervous system metronidazole-induced encephalopathy is a rare but serious condition. We performed a literature review of 34 cases including 2 of our cases, 25 from domestic conference abstracts, and 7 cases presented in full research papers. The mean patient age was 64.7 years. The conditions most commonly treated with metronidazole were brain abscess (35.3%), liver abscess (17.6%), and Clostridium difficile infection (14.7%). The most common predisposing conditions were liver dysfunction (26.5%), diabetes and other metabolic disorders (20.6%), and hematologic or solid organ malignancy (14.7%). The mean period of administration before the onset of encephalopathy symptoms was 61.3 days, and the mean total dose was 95.9g. The initial chief complaints were dysarthria (in 70.6% of the cases) and ataxia (61.8%); 82.4% of the cases were diagnosed on the basis of MRI (T2-weighted or FLAIR imaging). The key imaging finding was high intensity in the dentate nucleus bilaterally (82.4%). Stopping the metronidazole led to symptom remission within 8.5 days, but the MRI changes remained longer than the clinical symptoms. Two patients (6.0%) developed irreversible disturbance of consciousness. Although the mechanisms of this type of encephalopathy have not yet been elucidated, localized nerve-cell edema is likely caused by decreased metronidazole metabolism associated with liver and metabolic dysfunction. Careful observation for neurologic signs should be conducted during the treatment of brain abscesses associated with metronidazole administration, because patients with brain abscesses are naturally at high risk of metronidazole-induced encephalopathy

  4. Resistance of Trichomonas vaginalis to Metronidazole: Report of the First Three Cases from Finland and Optimization of In Vitro Susceptibility Testing under Various Oxygen Concentrations

    PubMed Central

    Meri, Taru; Jokiranta, T. Sakari; Suhonen, Lauri; Meri, Seppo

    2000-01-01

    Trichomonas vaginalis is a globally common sexually transmitted human parasite. Many strains of T. vaginalis from around the world have been described to be resistant to the current drug of choice, metronidazole. However, only a few cases of metronidazole resistance have been reported from Europe. The resistant strains cause prolonged infections which are difficult to treat. T. vaginalis infection also increases the risk for human immunodeficiency virus transmission. We present a practical method for determining the resistance of T. vaginalis to 5-nitroimidazoles. The suggested method was developed by determining the MICs and minimal lethal concentrations (MLCs) of metronidazole and ornidazole for T. vaginalis under various aerobic and anaerobic conditions. Using this assay we have found the first three metronidazole-resistant strains from Finland, although the origin of at least one of the strains seems to be Russia. Analysis of the patient-derived and previously characterized isolates showed that metronidazole-resistant strains were also resistant to ornidazole, and MLCs for all strains tested correlated well with the MICs. The suggested MICs of metronidazole for differentiation of sensitive and resistant isolates are >75 μg/ml in an aerobic 24-h assay and >15 μg/ml in an anaerobic 48-h assay. PMID:10655382

  5. Metronidazole and 5-aminosalicylic acid enhance the contractile activity of histaminergic agonists on the guinea-pig isolated ileum

    SciTech Connect

    Winbery, S.L.; Barker, L.A.

    1986-03-01

    The effects of metronidazole and 5-aminosalicylic acid (5-ASA) on histamine receptor-effector systems in the small intestine and right atrium of the guinea pig were studied. In an apparently all-or-none manner, both caused a sinistral shift in dose-response curves for the phasic component of the contractile response to histamine at H1 receptors on the ileum. In the presence of either, the EC50 value for histamine was reduced from 0.07 to about 0.03 microM. Similarly, in an apparently all-or-none fashion, both produced an elevation in the dose-response curve for the actions of dimaprit at H2-receptors in the ileum; the response to all doses was increased about 30% with no significant change in the EC50 value. Metronidazole and 5-ASA did not alter dose-response curves for the tonic contractile response to histamine or curves generated by the cumulative addition of histamine. Also, neither altered the positive chronotropic response on isolated right atria or the phasic contractile response on isolated segments of jejunum and duodenum to histamine or dimaprit. Likewise, neither altered dose-response curves for the direct action of carbamylcholine at muscarinic receptors or for the indirect actions of dimethylphenylpiperazinium on the ileum. The effects of 5-ASA or metronidazole on the response to histamine could be prevented as well as reversed by scopolamine or tetrodotoxin. The results suggest that metronidazole and 5-ASA enhance the actions of histamine and dimaprit on the ileum by an action on myenteric plexus neurons.

  6. Treatment of refractory Crohn's disease and pyoderma gangrenosum with a combination regimen of rifaximin, gentamicin and metronidazole.

    PubMed

    Goldberg, Neil D; Vadlamudi, Aravinda; Parrish, Nicole

    2015-01-01

    The etiology of Crohn's disease (CD) remains controversial. It is hypothesized that CD is the result of an abnormal immune response to the gut flora in genetically susceptible hosts. However, an infectious etiology has not been completely ruled out. Antibiotics have been utilized with some success to modify the course of the disease. Here, we report a patient with CD and pyoderma gangrenosum refractory to standard therapy, including biologics, who achieved remission with a combination of rifaximin, gentamicin and metronidazole. PMID:25802494

  7. Treatment of Refractory Crohn's Disease and Pyoderma Gangrenosum with a Combination Regimen of Rifaximin, Gentamicin and Metronidazole

    PubMed Central

    Goldberg, Neil D.; Vadlamudi, Aravinda; Parrish, Nicole

    2015-01-01

    The etiology of Crohn's disease (CD) remains controversial. It is hypothesized that CD is the result of an abnormal immune response to the gut flora in genetically susceptible hosts. However, an infectious etiology has not been completely ruled out. Antibiotics have been utilized with some success to modify the course of the disease. Here, we report a patient with CD and pyoderma gangrenosum refractory to standard therapy, including biologics, who achieved remission with a combination of rifaximin, gentamicin and metronidazole. PMID:25802494

  8. Enhanced ultrasound-assisted degradation of methyl orange and metronidazole by rectorite-supported nanoscale zero-valent iron.

    PubMed

    Yuan, Na; Zhang, Gaoke; Guo, Sheng; Wan, Zhen

    2016-01-01

    In this study, the rectorite-supported nanoscale zero-valent iron (nZVI/R) was synthesized through a reduction method. X-ray diffraction analysis showed the existence of the nZVI in the nZVI/R composite and X-ray photoelectron spectroscopy analysis indicated that the nZVI particles were partly oxidized into iron oxide. Scanning electron microscopy analysis revealed that the nZVI particles were highly dispersed on the surface of the rectorite. The specific surface area of the nZVI/R composite is 21.43 m(2)/g, which was higher than that of rectorite (4.30 m(2)/g) and nZVI (17.97 m(2)/g). In the presence of ultrasound (US), the degradation of methyl orange and metronidazole by the nZVI/R composite was over 93% and 97% within 20 min, respectively, which is much higher than that by the rectorite and the nZVI. The degradation ratio of methyl orange and metronidazole by the nZVI/R composite under US was 1.7 and 1.8 times as high as that by the nZVI/R composite without US, respectively. The mechanism of the enhanced degradation of methyl orange and metronidazole under US irradiation was studied. These results indicate that the US/nZVI/R process has great potential application value for treatment of dye wastewater and medicine wastewater. PMID:26384884

  9. Metronidazole reduces intestinal inflammation and blood loss in non-steroidal anti-inflammatory drug induced enteropathy.

    PubMed Central

    Bjarnason, I; Hayllar, J; Smethurst, P; Price, A; Gumpel, M J

    1992-01-01

    This study assessed the effect of metronidazole on the gastroduodenal mucosa, intestinal permeability, blood loss, and inflammation in patients on non-steroidal anti-inflammatory drugs (NSAIDs). Thirteen patients were studied before and after 2-12 weeks' treatment with metronidazole 800 mg/day, while maintaining an unchanged NSAID intake. Intestinal inflammation, as assessed by the faecal excretion of indium-111 labelled neutrophils, and blood loss, assessed with chromium-51 labelled red cells, were significantly reduced after treatment (mean (SD) 111In excretion 4.7 (4.7)% v 1.5 (1.3)% (N < 1.0%), p < 0.001, 51Cr red cells loss 2.6 (1.6) ml/day v 0.9 (0.5) ml/day (N < 1.0 ml/day), p < 0.01). Intestinal permeability assessed as the 5 hour urinary excretion ratio of 51CrEDTA/L-rhamnose did not change significantly (0.133 (0.046) v 0.154 (0.064), p > 0.1) and there were no significant changes in the endoscopic or microscopic appearances of the gastroduodenal mucosa. These results suggest that the neutrophil is the main damaging effector cell in NSAID induced enteropathy. The main neutrophil chemo-attractant in this enteropathy may be a metronidazole sensitive microbe. PMID:1427372

  10. Treatment of Bacterial Vaginosis: A Multicenter, Double-Blind, Double-Dummy, Randomised Phase III Study Comparing Secnidazole and Metronidazole

    PubMed Central

    Bohbot, Jean-Marc; Vicaut, Eric; Fagnen, Didier; Brauman, Michel

    2010-01-01

    Objective. Multiple-dose metronidazole oral therapy is currently the reference treatment for bacterial vaginosis (BV). This double-blind, double-dummy, noninferiority study compared the efficacy of secnidazole, another nitroimidazole with pharmacokinetics allowing a single dose regimen, to this standard treatment. Methods. A total of 577 patients were randomized to receive metronidazole (500 mg, b.i.d for seven days) or secnidazole (2 g, once). Therapeutic cure at D28 was defined as the resolution of vaginal discharge, positive KOH whiff test, vaginal pH >4.5 and Nugent score >7 on Gram-stained vaginal fluid. Results. According to this primary endpoint, the single-dose secnidazole regimen was shown to be at least as effective as the multiple-dose metronidazole regimen (60.1 % cured women vs 59.5% , 95% confidence interval with a noninferiority margin of 10%: [−0.082; 0.0094]). Safety profiles were comparable in both groups. Conclusion. The secnidazole regimen studied represents an effective, convenient therapeutic alternative that clinicians should consider in routine practice. PMID:20885970