scholarly journals In vitro pH dependent passive transport of ketoprofen and metformin

ADMET & DMPK ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 57-68
Author(s):  
Alisa Elezović ◽  
Amina Marić ◽  
Amila Biščević ◽  
Jasmina Hadžiabdić ◽  
Selma Škrbo ◽  
...  

The kinetics of passive transport of ketoprofen and metformin, as model substances for high and low permeability, respectively, across the artificial membrane under the influence of the pH of donor solution was investigated. There was an upward trend in the apparent permeation coefficient (Papp) of ketoprofen with the decrease in pH to a value close to pKa. At the pH value below pKa the permeation coefficient had lower value, due to the higher retention of ketoprofen in the artificial membrane. Metformin is a low permeable compound, and the highest permeation values were recorded at pH 7.4. Two dissociation constants determine that metformin at physiological pH exists as a hydrophilic cationic molecule, i.e. predominantly in ionized form. At pH values below 2.8, metformin mainly exists in diprotonated form, and it was, thus, very poorly permeable. The highest retention, i.e. affinity of both ketoprofen and metformin to the membrane, was at the lowest pH values, which is explained by different mechanisms. At higher pH values of the donor compartment, the substances showed significantly less affinity to the membrane. The obtained values of apparent permeation coefficients at studied pH values showed a good correlation with the obtained experimental values by other in vitro methods.    

1965 ◽  
Vol 43 (6) ◽  
pp. 661-670 ◽  
Author(s):  
W. H. Cook ◽  
R. A. Wallace

Dissociation of β-lipovitellin was detectable at pH 5.8 and increased linearly with pH. Light-scattering measurements at different pH values were consistent with a molecular weight of 2.27 × 105 for the subunit and twice this value for the associated form, confirming that it is a monomer–dimer system. This value for the molecular weight of the dimer is somewhat higher than previously reported (4.0 × 105) partly because a solvent displacement correction was used in estimating concentration by a dry weight method. Dissociation constants evaluated from light-scattering measurements and by ultracentrifugal separation were 22 × 10−6 and 29 × 10−6 respectively, in good agreement with provisional values already reported. Preliminary studies on the kinetics of this reaction indicate that, when the pH is altered, dissociation reaches the new equilibrium in about 0.5 minute but that reassociation requires about 50 minutes.


2015 ◽  
Vol 71 (9) ◽  
pp. 1340-1346 ◽  
Author(s):  
Jian Li ◽  
Tuqiao Zhang ◽  
Miaomiao Ye

Diclofenac (DCF), one of the pharmaceutical and personal care products that has been widely detected in water, was selected as a model pollutant to evaluate the oxidation activity of α-MnO2 nanorods. The results showed that the heterogeneous oxidation process is highly pH dependent, with higher degradation efficiency at lower pH values. The complete removal of DCF was obtained within 80 min at the solution pH value of 2.5. The oxidation kinetics of DCF can be modeled by Langmuir–Hinshelwood equation (R2 > 0.999). The effects of various operating parameters, including initial solution pH, α-MnO2 dosage, anions, and cations, on the oxidation efficiency were investigated in detail. A possible reaction pathway for DCF was proposed. In addition, it was demonstrated that the α-MnO2 nanorods can be recycled without decreasing their oxidation activity after 10 cycles.


1997 ◽  
Vol 321 (2) ◽  
pp. 481-486 ◽  
Author(s):  
Deborah H. SUTTON ◽  
Graeme L. CONN ◽  
Tom BROWN ◽  
Andrew N. LANE

We have developed a sensitive continuous assay for nucleases using proton release. The assay has been applied to the determination of the kinetics of DNase I acting on short, defined deoxyoligonucleotides. The dependence of kcat/Km on sequence and structure of short oligonucleotide substrates has been measured: increasing lengths of AnTn sequences decrease the rate of cleavage. GƃA mismatches in which the bases pair using imino protons are cleaved quite effectively by DNase I. In contrast, tandem GƃA mismatches which use amino pairing and have BII phosphodiesters, are refractory to DNase I. Also, the DNA strands of DNAƃRNA hybrid duplexes are not cleaved by DNase I. These results show that the global conformation of a duplex and the details of its minor groove affect the cleavage efficiency by DNase I. The assay has also been used to measure the inhibition constant of the minor-groove-binding ligand propamidine. A value of 3 ƁM has been determined for binding to the sequence d(CGCGAATTCGCG)2, showing that dissociation constants can be determined even when there are no convenient optical signals for titrations.


Nanomaterials ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 766
Author(s):  
Federica Vurro ◽  
Ylenia Jabalera ◽  
Silvia Mannucci ◽  
Giulia Glorani ◽  
Alberto Sola-Leyva ◽  
...  

Magnetococcus marinus magnetosome-associated protein MamC, expressed as recombinant, has been proven to mediate the formation of novel biomimetic magnetic nanoparticles (BMNPs) that are successful drug nanocarriers for targeted chemotherapy and hyperthermia agents. These BMNPs present several advantages over inorganic magnetic nanoparticles, such as larger sizes that allow the former to have larger magnetic moment per particle, and an isoelectric point at acidic pH values, which allows both the stable functionalization of BMNPs at physiological pH value and the molecule release at acidic (tumor) environments, simply based on electrostatic interactions. However, difficulties for BMNPs cell internalization still hold back the efficiency of these nanoparticles as drug nanocarriers and hyperthermia agents. In the present study we explore the enhanced BMNPs internalization following upon their encapsulation by poly (lactic-co-glycolic) acid (PLGA), a Food and Drug Administration (FDA) approved molecule. Internalization is further optimized by the functionalization of the nanoformulation with the cell-penetrating TAT peptide (TATp). Our results evidence that cells treated with the nanoformulation [TAT-PLGA(BMNPs)] show up to 80% more iron internalized (after 72 h) compared to that of cells treated with BMNPs (40%), without any significant decrease in cell viability. This nanoformulation showing optimal internalization is further characterized. In particular, the present manuscript demonstrates that neither its magnetic properties nor its performance as a hyperthermia agent are significantly altered due to the encapsulation. In vitro experiments demonstrate that, following upon the application of an alternating magnetic field on U87MG cells treated with BMNPs and TAT-PLGA(BMNPs), the cytotoxic effect of BMNPs was not affected by the TAT-PLGA enveloping. Based on that, difficulties shown in previous studies related to poor cell uptake of BMNPs can be overcome by the novel nanoassembly described here.


1956 ◽  
Vol 186 (2) ◽  
pp. 339-342 ◽  
Author(s):  
William J. Waddell

Dog erythrocytes undergo hemolysis in any isotonic medium with a value of ph higher than 7.6. The higher the value of ph, the more rapidly and the more completely hemolysis occurs; at ph 7.6 about 2 hours are required for noticeable hemolysis either in vivo or in vitro. This phenomenon does not occur with the erythrocytes of man, cat, mouse, guinea pig, rabbit, sheep, horse or ox. The erythrocytes of all species studied were seen to approach a spherical shape as the ph was increased above 7.5 and to become crenated at ph values below 7.3. The transition to a spherical shape in alkaline media is not due to an increase in volume but rather to a contraction of the surface membrane. It is suggested that the dog erythrocyte differs from that of other species in that its membrane can withstand less tension.


2017 ◽  
Vol 11 (2) ◽  
pp. 70
Author(s):  
Pramono A. ◽  
Kustono Kustono ◽  
D. T. Widayati ◽  
P. P. Putro ◽  
E. Handayanta ◽  
...  

The research aims to evaluate calsium soap protection as feed supplement based on dry matter<br />digestibility, organic matter digestibility and pH in vitro in the rumen and post rumen. Calsium soap<br />was produced from sardine fish oil and soybean meal, through two protection methods. It was<br />saponification and microencapsulation. This research used Split Subject Repeated Measurement<br />Design with 3 treatments (calcium soap, soybean meal and pangola grass) which each treatment was<br />repeated 5 times. The observation kinetics of dry matter digestibility, organic matter digestibility, and<br />pH rumen fluid were done in incubation times (2, 4, 8, 12, 24 and 48 hours respectively). The first<br />results of the research showed that in the first step (rumen) has dry matter digestibility of calcium<br />soaps: 38.65; 40.00; 42.66; 46.32; 54.40 and 51.40% respectively; organic matter digestibility: 39.44;<br />41.27; 44, 31; 46.32; 56.62 and 52.50% respectively. Kinetics of pH rumen fluid: 6.89; 6.79; 6.78;<br />6.74; 6.71, and 6.88 respectively. In the second step (post rumen), the digestibility of calsium soap<br />production has dry matter digestibility of 74.85% and organic matter of digestibilty of 72.94%. The<br />results could be concluded that in the rumen, calcium soap is the most microbial degradation resistant<br />compared the others and it can be degraded and digested in the abomasum to the small intestine.<br />Therefore pH of rumen fluid is optimal, so it does not interfere with the fermentation in the rumen.<br />Keywords: calsium soap, in vitro, dry matter digestibily, organic matter digestibility, pH value


2019 ◽  
Vol 40 (2) ◽  
pp. 831 ◽  
Author(s):  
Luiz Juliano Valério Geron ◽  
Luiz Eduardo Cantão Veloso ◽  
Sílvia Cristina de Aguiar ◽  
Alexandre Lima de Souza ◽  
Ilda dos Santos Souza ◽  
...  

The effect of inclusion of Morinda citrifolia L. (Noni) in standardized diets of sheep on in vitro digestibility and parameters fermentation was examined using two different inoculums (ruminal liquid and sheep feces). To determine the nutrients’ in vitro digestibility coefficient (IVDC), two sheep were used as inoculum donors. The experimental design was factorial (4 × 2), with four diets containing different proportions of Noni and two types of inoculum. The different dietary proportions of Noni (0%, 8%, 16%, and 24%) did not affect the IVDC of dry matter (DM), organic matter (OM) and crude protein (CP) for both inoculums. The IVDC of neutral detergent fiber (NDF) differed significantly between the inoculums. After in vitro incubation for 24 h, the pH value of the fermented material differed between the different diets and between the inoculums. Moreover, the concentration of ammoniacal nitrogen was affected by the proportion of Noni and differed between the inoculums after incubation for 24 h. The inclusion of up to 24% of Noni in standardized rations for ruminants did not affect the IVDC of DM, OM, CP, and NDF. The use of feces as inoculum for in vitro fermentation produced lower IVDC values than those by ruminal liquid. The diet containing 8% of Noni and fermented with ruminal liquid produced higher pH values after 24 h of incubation. Taken together, the different dietary Noni proportions and the different inoculums can alter the concentration of ammoniacal nitrogen of sheep diets after 24 h in vitro fermentation; however, they seem not to affect the IVDC of the nutrients.


2010 ◽  
Vol 62 (4) ◽  
pp. 915-934 ◽  
Author(s):  
S. Ivancajic ◽  
I. Mileusnic ◽  
Desanka Cenic-Milosevic

This research investigated the effects of propolis extracted by 5 different solvents and aged for 7 days on twelve species of bacteria classified into four groups according to their pathogenicity in slightly acidic (pH=6), neutral (pH=7) and slightly alkaline (pH=8) environments. Propolis extracted by the examined solvents had antibacterial effects. The strongest effects on the growth of all tested microorganisms, except on the bacteria of the Salmonella genus, regardless of the pH value of the environment, were exerted by propolis extracted by ether, acetone, toluol and chloroform. In some cases the antibacterial action of propolis was best in a slightly acidic environment (pH=6).


2019 ◽  
Vol 63 (5) ◽  
Author(s):  
E. L. Larkin ◽  
L. Long ◽  
N. Isham ◽  
K. Borroto-Esoda ◽  
S. Barat ◽  
...  

ABSTRACT Ibrexafungerp (IBX) (formerly SCY-078) is a novel glucan synthase inhibitor whose oral availability is being evaluated for efficacy against vulvovaginal candidiasis (VVC). Bioavailability and in vitro activity are important efficacy indicators, but accepted susceptibility methods do not always accurately predict activity in an acidic environment, such as the vagina. Studies were 3-fold, as follows: (i) pharmacokinetic study following oral administration in a murine model; (ii) susceptibility testing of isolates from a phase 2 VVC clinical trial by CLSI M27-A4 methodology; and (iii) susceptibility testing of Candida albicans and Candida glabrata isolates obtained from this trial group in RPMI 1640 adjusted to 3 different pH values, 7.0, 5.72, and 4.5, compared to susceptibility testing for micafungin and fluconazole. IBX readily accumulated in vaginal tissues and secretions following oral administration. Potent in vitro activity was demonstrated against Candida strains obtained at baseline and end of study visits. Moreover, the geometric mean (GM) values for IBX at pH 4.5 were dramatically lower than those at pH 7.0 and 5.72. The MIC90 values of micafungin remained the same regardless of pH value, while those of fluconazole tended to increase with lower pH values. IBX is able to reach target tissues following oral administration at pharmacologically meaningful levels. IBX demonstrated potent in vitro activity, with no development of resistance, following repeated exposure over the course of the clinical trial. Importantly, activity of IBX in an acidic medium suggests a therapeutic advantage of this novel antifungal in the treatment of vaginal Candida infections.


2021 ◽  
Author(s):  
Carlotta Carlini ◽  
Antonio Primante ◽  
Nicolas Greggio ◽  
Enrico Balugani ◽  
Andrea Contin ◽  
...  

&lt;p&gt;The recovery of PO&lt;sub&gt;4&lt;/sub&gt; from wastewaters by using biochar proves not to be completely satisfactory. The surface of the biochar is typically negatively charged, which prevents the adsorption of PO&lt;sub&gt;4&lt;/sub&gt;. For this reason, mixtures of biochar and natural carbonate materials have been tested as a novel sorbent material for PO&lt;sub&gt;4 &lt;/sub&gt;recovery from both synthetic-and waste- water. The goal of the research is to obtain a PO&lt;sub&gt;4 &lt;/sub&gt;based complex starting from natural second-generation materials such as food industry byproducts, plants and other residues to prepare fertilisers compliant to the component material category CMC 6 defined in the Regulation &lt;strong&gt;(&lt;/strong&gt;EU) 2019/1009/EU It has to be noted that natural carbonate materials are not pure CaCO&lt;sub&gt;3&lt;/sub&gt;, but present small impurities that contribute to modify their properties. Therefore, the use of carbonate materials obtained from different sources can lead to different performances when it comes to PO&lt;sub&gt;4&lt;/sub&gt; removal from wastewaters.&lt;/p&gt;&lt;p&gt;In this work we present results of PO&lt;sub&gt;4&lt;/sub&gt; removal obtained from a mixture of biomass and different carbonate materials. The mixture has been treated through a specific thermal protocol to obtain two different calcium-oxide rich charcoals here named composites C1 and C2. Initially, each composite was added to synthetic waters with different PO&lt;sub&gt;4 &lt;/sub&gt;concentration, with a composite:water ratio of 1:1000. The initial concentrations of PO&lt;sub&gt;4 &lt;/sub&gt;were 10, 100 and 1000 mg/l. After treatment with the composite, regardless of whether C1 or C2 was used, the PO&lt;sub&gt;4 &lt;/sub&gt;concentration in the waters with initial concentration of 10 and 100 mg/L was nearly zero, with pH values at equilibrium around 11.9. The treatment of the water with initial PO&lt;sub&gt;4 &lt;/sub&gt;concentration of 1000 mg/l shows a reduction of 20% and 40% with C1 and C2, respectively, with final pH values around 7.8.&lt;/p&gt;&lt;p&gt;After addition of the composites to the water, the solutions present very high pH values except for the water with the highest concentration. Although this is an optimal situation for the removal of PO&lt;sub&gt;4&lt;/sub&gt;, it leads to two problems. First, the filtered water is not suitable for direct disposition in sewers, since the pH is higher than the limit established by the wastewater legislation (9.5). Second, a pH value larger than 9 determines the precipitation of PO&lt;sub&gt;4 &lt;/sub&gt;regardless of the presence of the composite, which suggests that the PO&lt;sub&gt;4&lt;/sub&gt; is not adsorbed by the composites, thus not leading to the desired complex&lt;/p&gt;&lt;p&gt;In order to quantify the exact amount of PO&lt;sub&gt;4&lt;/sub&gt; adsorbed by the composite, the experiments have been repeated under controlled pH, keeping it around a value of 7 by the use of a mild acid. In this condition, after 1h treatment, 50% of phosphate was removed and bound to the composite&lt;/p&gt;&lt;p&gt;The work intends to present the results at laboratory scale and next steps at higher TRL.&lt;/p&gt;


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