scholarly journals Liposome-Encapsulated Bacteriophages for Enhanced Oral Phage Therapy against Salmonella spp.

2015 ◽  
Vol 81 (14) ◽  
pp. 4841-4849 ◽  
Author(s):  
Joan Colom ◽  
Mary Cano-Sarabia ◽  
Jennifer Otero ◽  
Pilar Cortés ◽  
Daniel Maspoch ◽  
...  
Keyword(s):  
Intestinal Tract ◽  
Positive Charge ◽  
Phage Therapy ◽  
Gastric Fluid ◽  
Simulated Gastric Fluid ◽  
Salmonella Spp ◽  
Content Type ◽  
The Difference ◽  
Over Time

ABSTRACTBacteriophages UAB_Phi20, UAB_Phi78, and UAB_Phi87 were encapsulated in liposomes, and their efficacy in reducingSalmonellain poultry was then studied. The encapsulated phages had a mean diameter of 309 to 326 nm and a positive charge between +31.6 and +35.1 mV (pH 6.1). In simulated gastric fluid (pH 2.8), the titer of nonencapsulated phages decreased by 5.7 to 7.8 log units, whereas encapsulated phages were significantly more stable, with losses of 3.7 to 5.4 log units. The liposome coating also improved the retention of bacteriophages in the chicken intestinal tract. When cocktails of the encapsulated and nonencapsulated phages were administered to broilers, after 72 h the encapsulated phages were detected in 38.1% of the animals, whereas the nonencapsulated phages were present in only 9.5%. The difference was significant. In addition, in anin vitroexperiment, the cecal contents of broilers promoted the release of the phages from the liposomes. In broilers experimentally infected withSalmonella, the daily administration of the two cocktails for 6 days postinfection conferred similar levels of protection againstSalmonellacolonization. However, once treatment was stopped, protection by the nonencapsulated phages disappeared, whereas that provided by the encapsulated phages persisted for at least 1 week, showing the enhanced efficacy of the encapsulated phages in protecting poultry againstSalmonellaover time. The methodology described here allows the liposome encapsulation of phages of different morphologies. The preparations can be stored for at least 3 months at 4°C and could be added to the drinking water and feed of animals.

scholarly journals Bioelution, Bioavailability, and Toxicity of Cobalt Compounds Correlate

2020 ◽  
Vol 174 (2) ◽  
pp. 311-325 ◽  
Author(s):  
Ruth Danzeisen ◽  
David Lee Williams ◽  
Vanessa Viegas ◽  
Michael Dourson ◽  
Steven Verberckmoes ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Gastric Fluid ◽  
Simulated Gastric Fluid ◽  
In Vivo Toxicity ◽  
Invaluable Tool ◽  
Adverse Effect Level ◽  
In Vitro Bioaccessibility ◽  
The Difference

Abstract Based on the wide use of cobalt substances in a range of important technologies, it has become important to predict the toxicological properties of new or lesser-studied substances as accurately as possible. We studied a group of 6 cobalt substances with inorganic ligands, which were tested for their bioaccessibility (surrogate measure of bioavailability) through in vitro bioelution in simulated gastric and intestinal fluids. Representatives of the group also underwent in vivo blood kinetics and mass balance tests, and both oral acute and repeated dose toxicity (RDT) testing. We were able to show a good correlation between high in vitro bioaccessibility with high in vivo bioavailability and subsequent high in vivo toxicity; consequently, low in vitro bioaccessibility correlated well with low in vivo bioavailability and low in vivo toxicity. In vitro bioelution in simulated gastric fluid was the most precise predictor of the difference in the oral RDT lowest observed adverse effect levels of 2 compounds representing the highly and poorly bioaccessible subset of substances. The 2 compounds cobalt dichloride hexahydrate and tricobalt tetraoxide differed by a factor of 440 in their in vitro bioaccessibility and by a factor of 310 in their RDT lowest observed adverse effect level. In summary, this set of studies shows that solubility, specifically in vitro bioelution in simulated gastric fluid, is a good, yet conservative, predictor of in vivo bioavailability and oral systemic toxicity of inorganic cobalt substances. Bioelution data are therefore an invaluable tool for grouping and read across of cobalt substances for hazard and risk assessment.

scholarly journals Listeria monocytogenes Strains Underrepresented during Selective Enrichment with an ISO Method Might Dominate during Passage through Simulated Gastric Fluid andIn VitroInfection of Caco-2 Cells

2016 ◽  
Vol 82 (23) ◽  
pp. 6846-6858 ◽  
Author(s):  
Evangelia Zilelidou ◽  
Christina-Vasiliki Karmiri ◽  
Georgia Zoumpopoulou ◽  
Eleni Mavrogonatou ◽  
Dimitris Kletsas ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Gastric Fluid ◽  
Simulated Gastric Fluid ◽  
Simultaneous Exposure ◽  
Relative Population ◽  
Content Type ◽  
Selective Enrichment ◽  
Outbreak Investigations ◽  
Multiple Strains

ABSTRACTVariousListeria monocytogenesstrains may contaminate a single food product, potentially resulting in simultaneous exposure of consumers to multiple strains. However, due to bias in strain recovery,L. monocytogenesstrains isolated from foods by selective enrichment (SE) might not always represent those that can better survive the immune system of a patient. We investigated the effect of cocultivation in tryptic soy broth with 0.6% yeast extract (TSB-Y) at 10°C for 8 days on (i) the detection ofL. monocytogenesstrains during SE with the ISO 11290-1:1996/Amd 1:2004 protocol and (ii) thein vitrovirulence of strains toward the Caco-2 human colon epithelial cancer cell line following exposure to simulated gastric fluid (SGF; pH 2.0)-HCl (37°C). We determined whether the strains which were favored by SE would be effective competitors under the conditions of challenges related to gastrointestinal passage of the pathogen. Interstrain competition ofL. monocytogenesin TSB-Y determined the relative population of each strain at the beginning of SE. This in turn impacted the outcome of SE (i.e., favoring survival of competitors with better fitness) and the levels exposed subsequently to SGF. However, strong growth competitors could be outcompeted after SGF exposure and infection of Caco-2 cells by strains outgrown in TSB-Y and underdetected (or even missed) during enrichment. Our data demonstrate a preferential selection of certainL. monocytogenesstrains during enrichments, often not reflecting a selective advantage of strains during infection. These findings highlight a noteworthy scenario associated with the difficulty of matching the source of infection (food) with theL. monocytogenesisolate appearing to be the causative agent during listeriosis outbreak investigations.IMPORTANCEThis report is relevant to understanding the processes involved in selection and prevalence of certainL. monocytogenesstrains in different environments (i.e., foods or sites of humans exposed to the pathogen). It highlights the occurrence of multiple strains in the same food as an important aspect contributing to mismatches between clinical isolates and infection sources during listeriosis outbreak investigations.

scholarly journals Formulation of Quaternized Aminated Chitosan Nanoparticles for Efficient Encapsulation and Slow Release of Curcumin

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 449
Author(s):  
Ahmed M. Omer ◽  
Zyta M. Ziora ◽  
Tamer M. Tamer ◽  
Randa E. Khalifa ◽  
Mohamed A. Hassan ◽  
...  
Keyword(s):  
Slow Release ◽  
Sodium Tripolyphosphate ◽  
Chitosan Nanoparticles ◽  
Gastric Fluid ◽  
Release Profile ◽  
Simulated Gastric Fluid ◽  
Maximum Value ◽  
Structure Surface ◽  
Drug Encapsulation Efficiency

An effective drug nanocarrier was developed on the basis of a quaternized aminated chitosan (Q-AmCs) derivative for the efficient encapsulation and slow release of the curcumin (Cur)-drug. A simple ionic gelation method was conducted to formulate Q-AmCs nanoparticles (NPs), using different ratios of sodium tripolyphosphate (TPP) as an ionic crosslinker. Various characterization tools were employed to investigate the structure, surface morphology, and thermal properties of the formulated nanoparticles. The formulated Q-AmCs NPs displayed a smaller particle size of 162 ± 9.10 nm, and higher surface positive charges, with a maximum potential of +48.3 mV, compared to native aminated chitosan (AmCs) NPs (231 ± 7.14 nm, +32.8 mV). The Cur-drug encapsulation efficiency was greatly improved and reached a maximum value of 94.4 ± 0.91%, compared to 75.0 ± 1.13% for AmCs NPs. Moreover, the in vitro Cur-release profile was investigated under the conditions of simulated gastric fluid [SGF; pH 1.2] and simulated colon fluid [SCF; pH 7.4]. For Q-AmCs NPs, the Cur-release rate was meaningfully decreased, and recorded a cumulative release value of 54.0% at pH 7.4, compared to 73.0% for AmCs NPs. The formulated nanoparticles exhibited acceptable biocompatibility and biodegradability. These findings emphasize that Q-AmCs NPs have an outstanding potential for the delivery and slow release of anticancer drugs.

scholarly journals Safety Assessment of Nano-Hydroxyapatite as an Oral Care Ingredient according to the EU Cosmetics Regulation

Cosmetics ◽  
2018 ◽  
Vol 5 (3) ◽  
pp. 53 ◽  
Author(s):  
Joana Ramis ◽  
Catarina Coelho ◽  
Alba Córdoba ◽  
Paulo Quadros ◽  
Marta Monjo
Keyword(s):  
Oral Care ◽  
Gastric Fluid ◽  
Gingival Tissue ◽  
Simulated Gastric Fluid ◽  
Tem Analysis ◽  
Consumer Safety ◽  
Transmission Electron ◽  
Dissolution Behaviour ◽  
Gingival Epithelium

Hydroxyapatite nanoparticles (HAP-NP) are incorporated in oral care products such as toothpastes and mouthwashes to treat dental sensitivity or to promote enamel remineralisation. Despite the good performance of HAP-NP in this application, it is important to ensure its safety for consumers. For that reason, the Scientific Committee on Consumer Safety (SCCS) evaluated the safety of HAP-NP as an oral care ingredient, but the issued opinion was not completely conclusive and the SCCS recommended that additional tests should be performed. Here, we used a commercially available human gingival epithelium (HGE) as a non-animal alternative and MTT cell viability, LDH activity, and IL-1alpha production were evaluated after 3.1% HAP-NP treatment for 10 min, 1 h, and 3 h. Moreover, the absorption of HAP-NP in the gingival tissue was assessed by transmission electron microscopy (TEM) analysis. Finally, the dissolution behaviour of HAP-NP in simulated gastric fluid was also investigated. No deleterious effect was observed for HGE tissues incubated with HAP-NP for all time-points and parameters evaluated. Moreover, a complete dissolution of 3.1% HAP-NP in simulated gastric fluid was observed after 7.5 min at 37 °C. In conclusion, our results evidence the safety of HAP-NP for oral care products with the use of an in vitro replacement alternative for human gingival epithelium and a simulated gastric fluid assay.

scholarly journals Advanced Quantification Methods To Improve the 18b Dormancy Model for Assessing the Activity of Tuberculosis Drugs In Vitro

2020 ◽  
Vol 64 (7) ◽  
Author(s):  
E. D. Pieterman ◽  
M. J. Sarink ◽  
C. Sala ◽  
S. T. Cole ◽  
J. E. M. de Steenwinkel ◽  
...  
Keyword(s):  
Drug Development ◽  
Area Under The Curve ◽  
High Dose ◽  
Current Form ◽  
Content Type ◽  
Solid Media ◽  
Development Pipeline ◽  
The Difference ◽  
Time Kill

ABSTRACT One of the reasons for the lengthy tuberculosis (TB) treatment is the difficulty to treat the nonmultiplying mycobacterial subpopulation. In order to assess the ability of (new) TB drugs to target this subpopulation, we need to incorporate dormancy models in our preclinical drug development pipeline. In most available dormancy models, it takes a long time to create a dormant state, and it is difficult to identify and quantify this nonmultiplying condition. The Mycobacterium tuberculosis 18b strain might overcome some of these problems, because it is dependent on streptomycin for growth and becomes nonmultiplying after 10 days of streptomycin starvation but still can be cultured on streptomycin-supplemented culture plates. We developed our 18b dormancy time-kill kinetics model to assess the difference in the activity of isoniazid, rifampin, moxifloxacin, and bedaquiline against log-phase growth compared to the nonmultiplying M. tuberculosis subpopulation by CFU counting, including a novel area under the curve (AUC)-based approach as well as time-to-positivity (TTP) measurements. We observed that isoniazid and moxifloxacin were relatively more potent against replicating bacteria, while rifampin and high-dose bedaquiline were equally effective against both subpopulations. Moreover, the TTP data suggest that including a liquid culture-based method could be of additional value, as it identifies a specific mycobacterial subpopulation that is nonculturable on solid media. In conclusion, the results of our study underline that the time-kill kinetics 18b dormancy model in its current form is a useful tool to assess TB drug potency and thus has its place in the TB drug development pipeline.

scholarly journals Ciclopirox and Efinaconazole Transungual Permeation, Antifungal Activity, and Proficiency To Induce Resistance in Trichophyton rubrum

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Daniela Monti ◽  
Diletta Mazzantini ◽  
Silvia Tampucci ◽  
Alessandra Vecchione ◽  
Francesco Celandroni ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Trichophyton Rubrum ◽  
Nail Plate ◽  
Content Type ◽  
Nail Bed ◽  
Antimycotic Activity ◽  
Frequent Relapses ◽  
Induce Resistance ◽  
Over Time

ABSTRACT Onychomycosis is a nail fungal infection, mostly caused by dermatophytes. The treatment efficacy is impaired by difficulties of reaching effective drug levels at the site of infection; frequent relapses occur after cessation of antifungal therapy. The aim of the study was to compare two commercial products containing ciclopirox or efinaconazole for antimycotic activity and antifungal drug resistance. A study of permeation and penetration through bovine hoof membranes, as a nail model, was performed to evaluate the antimycotic activity of permeates against clinical isolates of selected fungi, and the frequency of spontaneous in vitro Trichophyton rubrum-resistant strains was assessed by broth microdilution assays. The results suggest that ciclopirox creates a depot in the nail, leading to a gradual release of the drug over time with action on both the nail plate and bed. Conversely, efinaconazole, mildly interacting with nail keratin, mainly exerts its antifungal activity in the nail bed. However, in the case of T. rubrum, the antifungal activities of the drugs in the nail plate seem comparable. Finally, efinaconazole showed a potential for induction of resistance in T. rubrum, which may limit its efficacy over time. Ciclopirox did not show any potential to induce resistance in T. rubrum and appears endowed with a more complete activity than efinaconazole in the management of onychomycosis as the nail keratin is a substrate for the growth of fungal cells, and the availability of drug in large concentration just in the nail bed may not be sufficient to guarantee the complete eradication of pathogens.

scholarly journals The tax gap as a public management instrument: application to wealth taxes

2019 ◽  
Vol 27 (81) ◽  
pp. 207-225
Author(s):  
José M. Durán-Cabré ◽  
Alejandro Esteller Moré ◽  
Mariona Mas-Montserrat ◽  
Luca Salvadori
Keyword(s):  
Public Management ◽  
Design Methodology ◽  
Relative Size ◽  
Tax Compliance ◽  
Content Type ◽  
Tax Gap ◽  
Wealth Tax ◽  
The Difference ◽  
Gift Tax ◽  
Over Time

Purpose The purpose of this paper is to study the concept of tax gap, that is the difference between the total amount of taxes collected and the total tax revenues that would be collected under full tax compliance. Design/methodology/approach The authors also present the methodology to estimate the gap for two taxes levied on wealth: the wealth tax and the inheritance and gift tax; both are administered in Spain by the regional tax authorities. Findings The authors point out that its estimation offers useful information about the relative size and nature of non-compliance, as well as its evolution over time. Likewise, the tax gap is a valuable instrument not only to define enforcement strategies of the tax administration but also to enhance its accountability. Nonetheless, the methodology used to estimate the tax gap and, consequently, the interpretation of the results is subject to limitations that are discussed in the paper. Originality/value Finally, the paper provides the results of the estimations obtained from using microdata: 44.34 per cent gap in the wealth tax and 41.26 per cent in the inheritance and gift tax.

scholarly journals THE USE OF CLINOPTILOLITES AS CARRIER OF METFORMIN HYDROCHLORIDE IN DRUG DELIVERY SYSTEM: IN VITRO DRUG RELEASE STUDY

2018 ◽  
Vol 11 (11) ◽  
pp. 285
Author(s):  
Putra Imwa ◽  
Kusumawati Igaw
Keyword(s):  
Drug Release ◽  
Gastric Fluid ◽  
Simulated Gastric Fluid ◽  
Metformin Hydrochloride ◽  
Simulated Intestinal Fluid ◽  
In Vitro Drug Release ◽  
Encapsulation Process ◽  
N2 Sorption ◽  
Metformin Hcl

Objective: As an antidiabetic drug, metformin hydrochloride (HCl) has been well known to possess low oral bioavailability and short half-life. In this study, we prepared the drug delivery system (DDS) of metformin HCl and clinoptilolite as its carrier. The in vitro drug release profile was further investigated.Methods: DDS was made by encapsulating metformin HCl on clinoptilolite using the wet impregnation method at various pH and initial concentration of metformin HCl. Fourier transform infrared spectrometer (FTIR), X-ray diffractometer (XRD), and N2 Sorption Analyzer were used to characterize the as-synthesized DDS. Drug release study was conducted by stirring the DDS in simulated gastric fluid and simulated intestinal fluid over 12 h.Results: The encapsulation process was achieved optimally at pH 7.0 and initial concentration of metformin HCl of 300 mg/l (CLI2-300 denoted DDS). The results of FTIR and N2 sorption analyzer confirmed the existence of metformin HCl on clinoptilolites. Meanwhile, the XRD result showed that the crystallinity of clinoptilolites remained unchanged after the encapsulation process. The cumulative drug release in the simulated gastric fluid was found to be higher than that in the simulated intestinal fluid, which indicated the potent influence of pH on the release properties of the drugs. The drug release kinetics of metformin HCl from clinoptilolite was best fitted into the Korsmeyer-Peppas model with non-Fickian transport mechanism.Conclusion: We found that clinoptilolite was suitable for DDS application, particularly as a carrier of metformin HCl.

scholarly journals Preparation, Characterization, and In Vitro Evaluation of Resveratrol-Loaded Cellulose Aerogel

Materials ◽  
2020 ◽  
Vol 13 (7) ◽  
pp. 1624
Author(s):  
Lili Qin ◽  
Xinyu Zhao ◽  
Yiwei He ◽  
Hongqiang Wang ◽  
Hanjing Wei ◽  
...  
Keyword(s):  
High Speed ◽  
Drug Carrier ◽  
Phosphate Buffer Solution ◽  
Gastric Fluid ◽  
Simulated Gastric Fluid ◽  
Oxidized Cellulose ◽  
Buffer Solution ◽  
Aggregation State ◽  
Cellulose Aerogel

Resveratrol is a natural active ingredient found in plants, which is a polyphenolic compound and has a variety of pharmaceutical uses. Resveratrol-loaded TEMPO-oxidized cellulose aerogel (RLTA) was prepared using a freeze-drying method, employing high speed homogenization followed by rapid freezing with liquid nitrogen. RLTAs were designed at varying drug–cellulose aerogel ratios (1:2, 2:3, 3:2, and 2:1). It could be seen via scanning electron microscopy (SEM) that Res integrated into TEMPO-oxidized cellulose (TC) at different ratios, which changed its aggregation state and turned it into a short rod-like structure. Fourier transform infrared (FTIR) spectra confirmed that the RLTAs had the characteristic peaks of TC and Res. In addition, X-ray diffraction (XRD) demonstrated that the grain size of RLTA was obviously smaller than that of pure Res. RLTAs also had excellent stability in both simulated gastric fluid and phosphate buffer solution. The drug release rate was initially completed within 5 h under a loading rate of 30.7 wt%. The results of an MTT assay showed the low toxicity and good biocompatibility of the RLTAs. TC aerogel could be a promising drug carrier that may be widely used in designing and preparing novel biomedicine.

scholarly journals Effects of Sequential and Simultaneous Applications of Bacteriophages on Populations of Pseudomonas aeruginosaIn Vitroand in Wax Moth Larvae

2012 ◽  
Vol 78 (16) ◽  
pp. 5646-5652 ◽  
Author(s):  
Alex R. Hall ◽  
Daniel De Vos ◽  
Ville-Petri Friman ◽  
Jean-Paul Pirnay ◽  
Angus Buckling
Keyword(s):  
Bacterial Infections ◽  
Phage Therapy ◽  
Phage Type ◽  
Resistant Bacteria ◽  
Short Term ◽  
Short Term Treatment ◽  
Simultaneous Application ◽  
Content Type ◽  
Wax Moth

ABSTRACTInterest in using bacteriophages to treat bacterial infections (phage therapy) is growing, but there have been few experiments comparing the effects of different treatment strategies on both bacterial densities and resistance evolution. While it is established that multiphage therapy is typically more effective than the application of a single phage type, it is not clear if it is best to apply phages simultaneously or sequentially. We tried single- and multiphage therapy againstPseudomonas aeruginosaPAO1in vitro, using different combinations of phages either simultaneously or sequentially. Across different phage combinations, simultaneous application was consistently equal or superior to sequential application in terms of reducing bacterial population density, and there was no difference (on average) in terms of minimizing resistance. Phage-resistant bacteria emerged in all experimental treatments and incurred significant fitness costs, expressed as reduced growth rate in the absence of phages. Finally, phage therapy increased the life span of wax moth larvae infected withP. aeruginosa, and a phage cocktail was the most effective short-term treatment. When the ratio of phages to bacteria was very high, phage cocktails cured otherwise lethal infections. These results suggest that while adding all available phages simultaneously tends to be the most successful short-term strategy, there are sequential strategies that are equally effective and potentially better over longer time scales.

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