scholarly journals β-Cyclodextrin as a Functional Excipient Used for Enhancing the Diminazene Aceturate Bioavailability

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 295 ◽  
Author(s):  
Narcisa Marangoci ◽  
Daniel Timpu ◽  
Andreia Corciova ◽  
Cornelia Mircea ◽  
Anca-Roxana Petrovici ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Inclusion Complex ◽  
Blood Plasma ◽  
1H Nmr ◽  
Molar Ratio ◽  
Variation Method ◽  
In Vitro Tests ◽  
Diminazene Aceturate

In this study, we proposed formulations of diminazene aceturate (DA) designed to improve its bioavailability and to maximize the therapeutic index in animals by overcoming the rapid degradation under the acidic pH of the stomach. An important consequence is the fact that its amount in the bloodstream is close to the administered dose. This was made possible by incorporating DA into the β-cyclodextrin’s (βCD) cavity in a molar ratio of 1:1. The structure of the resulted inclusion complex was established by Raman, DSC, and Wide-Angle X ray Diffraction (WAXD) in solid state and by 1H-NMR and H-H ROESY in aqueous solutions. The stoichiometry of the DA:βCD inclusion complex was obtained by using the continuous variation method (Job’s plot), considering the chemical shifts variations of protons from both DA and βCD compounds in 1H-NMR spectra. The biological activity was estimated in vitro by antioxidant activity and in vivo by comparing the bioavailability of parent DA and its inclusion complexes after a single dose administration in Wistar rats by using the HPLC method on their blood plasma. In vitro tests showed an improved antioxidant activity. In vivo tests have shown that the DA concentration is always much higher in blood plasma of rats when DA:βCD inclusion complex of 1:1 molar ratio was administered (i.e., at 60 min, DA is around 11 and 3 times higher when DA:βCD inclusion complex of 1:1 molar ratio was administered than the parent DA one and DA:βCD lyophilized mixture of 1:2 molar ratio, respectively).

scholarly journals Effect of the cholesterol content of small unilamellar liposomes on their stability in vivo and in vitro

1980 ◽  
Vol 186 (2) ◽  
pp. 591-598 ◽  
Author(s):  
Christopher Kirby ◽  
Jacqui Clarke ◽  
Gregory Gregoriadis
Keyword(s):  
Blood Plasma ◽  
Intravenous Injection ◽  
Whole Blood ◽  
Cholesterol Content ◽  
Molar Ratio ◽  
Phosphatidylcholine Liposomes ◽  
Effective Use ◽  
Positively Charged

Small unilamellar neutral, negatively and positively charged liposomes composed of egg phosphatidylcholine, various amounts of cholesterol and, when appropriate, phosphatidic acid or stearylamine and containing 6-carboxyfluorescein were injected into mice, incubated with mouse whole blood, plasma or serum or stored at 4°C. Liposomal stability, i.e. the extent to which 6-carboxyfluorescein is retained by liposomes, was dependent on their cholesterol content. (1) Cholesterol-rich (egg phosphatidylcholine/cholesterol, 7:7 molar ratio) liposomes, regardless of surface charge, remained stable in the blood of intravenously injected animals for up to at least 400min. In addition, stability of cholesterol-rich liposomes was largely maintained in vitro in the presence of whole blood, plasma or serum for at least 90min. (2) Cholesterol-poor (egg phosphatidylcholine/cholesterol, 7:2 molar ratio) or cholesterol-free (egg phosphatidylcholine) liposomes lost very rapidly (at most within 2min) much of their stability after intravenous injection or upon contact with whole blood, plasma or serum. Whole blood and to some extent plasma were less detrimental to stability than was serum. (3) After intraperitoneal injection, neutral cholesterol-rich liposomes survived in the peritoneal cavity to enter the blood circulation in their intact form. Liposomes injected intramuscularly also entered the circulation, although with somewhat diminished stability. (4) Stability of neutral and negatively charged cholesterol-rich liposomes stored at 4°C was maintained for several days, and by 53 days it had declined only moderately. Stored liposomes retained their unilamellar structure and their ability to remain stable in the blood after intravenous injection. (5) Control of liposomal stability by adjusting their cholesterol content may help in the design of liposomes for effective use in biological systems in vivo and in vitro.

scholarly journals Comparative Characteristics of Determination of Antioxidant Activity of Sea Buckthorn Fruits by Various Methods

2019 ◽  
Vol 8 (4) ◽  
pp. 48-52
Author(s):  
O. V. Trineeva
Keyword(s):  
Antioxidant Activity ◽  
Medicinal Plant ◽  
Plant Material ◽  
Natural Antioxidants ◽  
Sea Buckthorn ◽  
In Vitro Tests ◽  
Medicinal Plant Material

Introduction. Recently, much attention has been paid to the primary assessment of the pharmacological effect of various drugs using in vivo and in vitro tests. It is known that such a medicinal plant as sea buckthorn, in its phytochemical composition is rich in natural antioxidants: carotenoids, tocopherols, flavonoids, ascorbic acid, etc. In some publications there is information about the antioxidant activity of sea buckthorn and fatty oil based on them. However, information on the comparative characteristics of the use of various methods for determining the antioxidant activity of this type of medicinal plant material and the results obtained are not found in the scientific literature.Aim. The aim of this work was a comparative determination of the antioxidant activity of medicinal plant material of buckthorn fruits of various species of buckthorn.Materials and methods. The total antioxidant activity of water and water-alcohol extracts from the fruits of sea buckthorn fruits was determined using various techniques recommended in the literature. The antioxidant activity of the extracts was determined by permanganometric titration, in vitro inhibition of adrenaline autooxidation, and also in a biological model, Parametium caudatum cell culture.Results and discussion. The effect of the extractant polarity on the value of antioxidant activity was studied. It was found that the highest content of antioxidants in the extraction is observed when using 96 % ethanol as an extractant.Conclusion. Using three methods, the prospects of using sea buckthorn fruits and preparations based on them as a source of antioxidants are shown. 

scholarly journals Complex Formation of Fibrin Monomers Studied by Gel Filtration and Polyacrylamide Gel Electrophoresis

1977 ◽  
Author(s):  
R. Hafter ◽  
M. Baumgärtner ◽  
R. v.Hugo ◽  
H. Graeff
Keyword(s):  
Complex Formation ◽  
Gel Electrophoresis ◽  
Polyacrylamide Gel Electrophoresis ◽  
Gel Filtration ◽  
Molecular Structures ◽  
Molar Ratio ◽  
In Vitro Tests ◽  
Fibrin Monomers

Estimation and characterization of thrombin mediated products of fibrinogen (soluble fibrin monomer complexes=SFMC) can be achieved by gel filtration and PAA-gel electrophoresis. In order to gain further information about complex formation in vitro tests were performed. Fibrin monomers were prepared from fibrin dissolved in 3 M KBr after action of thrombin (des-AB-fibrin) and reptilase (des-A-fibrin) on fibrinogen and added to plasma. In a certain range of fibrin concentration (up to 3% for des-AB-fibrin and up to 15% for des-A-fibrin) soluble complexes are formed with fibrinogen in a 1:1 molar ratio. Further increase of fibrin percentage results in a partial precipitation of complexes. Additionally, a marked increase of SFMC (up to 60 %) is observed with des-A-fibrin. This latter reaction indicates complex formation with a higher ratio of fibrinogen involved. An influence of temperature on complex forming could be observed. Gel filtration at 37°C reveals a shift in the elu-tion profile, indicating dissociation of high molecular weight complexes (5 million daltons) to lower molecular structures. The dissociation behaviour of SFMC from plasma samples of patients with hypercoagulability is similar. However, crosslinked fibrinoligomers showed no temperature dependant dissociation behaviour. It is concluded that SFMC exist during the state of hypercoagulability in vivo predominantly as a dimeric fibrin-fibrinogen complex.

scholarly journals Neuroprotective and Antioxidant Enhancing Properties of Selective Equisetum Extracts

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2565
Author(s):  
Denisa Batir-Marin ◽  
Monica Boev ◽  
Oana Cioanca ◽  
Cornelia Mircea ◽  
Ana Flavia Burlec ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
High Performance ◽  
Chemical Characterization ◽  
Biological Action ◽  
Neuroprotective Activity ◽  
In Vitro Tests ◽  
Skin Conditions ◽  
Tract Infections

The sterile stems belonging to the Equisetum species are often used in traditional medicine of various nations, including Romanians. They are highly efficient in treating urinary tract infections, cardiovascular diseases, respiratory tract infections, and medical skin conditions due to their content of polyphenolic derivatives that have been isolated. In this regard, this study aimed to provide the chemical composition of the extracts obtained from the Equisetum species (E. pratense, E. sylvaticum, E. telmateia) and to investigate the biological action in vitro and in vivo. For the chemical characterization of the analyzed Equisetum species extracts, studies were performed by using ultra-high-performance liquid chromatography (UHPLC-DAD). In vitro evaluation of the antioxidant activity of the plant extracts obtained from these species of Equisetum genus was determined. The neuroprotective activity of these three ethanolic extracts from the Equisetum species using zebrafish tests was determined in vivo. All obtained results were statistically significant. The results indicate that E. sylvaticum extract has a significant antioxidant activity; whereas, E. pratense extract had anxiolytic and antidepressant effects significantly higher than the other two extracts used. All these determinations indicate promising results for the antioxidant in vitro tests and neuroprotective activity of in vivo tests, particularly mediated by their active principles.

scholarly journals Effects of the Hydroethanolic Extract of Lycopodium selago L. on Scopolamine-Induced Memory Deficits in Zebrafish

2021 ◽  
Vol 14 (6) ◽  
pp. 568
Author(s):  
Mihai-Vlad Valu ◽  
Catalin Ducu ◽  
Sorin Moga ◽  
Denis Negrea ◽  
Lucian Hritcu ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Nutritive Value ◽  
Huperzine A ◽  
In Vitro Tests ◽  
Ultrasound Assisted Extraction ◽  
Zebrafish Model ◽  
Spectrophotometric Methods ◽  
Hydroethanolic Extract

This scientific research focused on the production of hydroethanolic extract of the plant species Lycopodium selago L. (L. selago) by the ultrasound-assisted extraction (USAE) and the identification of biocompounds with high antioxidant activity is of interest for possible phytotherapeutic treatment against Alzheimer’s disease (AD). The extract was phytochemically analyzed to investigate polyphenols, flavonoids, and identify the sesquiterpenoid alkaloid huperzine A (HupA), which is known in the literature for its great relevance in AD. Evaluation and comparison of the antioxidant activity of the extract were performed by four complementary spectrophotometric methods (DPPH, FRAP, ABTS, ORAC). In vitro tests of the extract showed an excellent reciprocal link between the concentration of polyphenols and the measurement of the antioxidant activity of the extract with the sesquiterpenoid HupA. To confirm the antioxidant activity, L. selago hydroethanolic extract was administered in vivo to zebrafish (Danio rerio) with a pattern of scopolamine-induced cognitive impairment. Moreover, this study explored a possible correlation between the expression of oxidative stress markers in the brain tissue with the behavior of the scopolamine zebrafish model. In vivo tests showed that this fern could be used as a nutritional supply and as a phytotherapeutic method to prevent or treat various neurodegenerative diseases that call for high-nutritive-value medications.

Comparison of High Purity Factor IX Concentrates and a Prothrombin Complex Concentrate in a Canine Model of Thrombogenicity

1991 ◽  
Vol 66 (05) ◽  
pp. 609-613 ◽  
Author(s):  
I R MacGregor ◽  
J M Ferguson ◽  
L F McLaughlin ◽  
T Burnouf ◽  
C V Prowse
Keyword(s):  
High Purity ◽  
Time Course ◽  
Prothrombin Complex Concentrate ◽  
Degradation Products ◽  
Canine Model ◽  
Factor Ix ◽  
In Vitro Tests ◽  
Albumin Infusion

SummaryA non-stasis canine model of thrombogenicity has been used to evaluate batches of high purity factor IX concentrates from 4 manufacturers and a conventional prothrombin complex concentrate (PCC). Platelets, activated partial thromboplastin time (APTT), fibrinogen, fibrin(ogen) degradation products and fibrinopeptide A (FPA) were monitored before and after infusion of concentrate. Changes in FPA were found to be the most sensitive and reproducible indicator of thrombogenicity after infusion of batches of the PCC at doses of between 60 and 180 IU/kg, with a dose related delayed increase in FPA occurring. Total FPA generated after 100-120 IU/kg of 3 batches of PCC over the 3 h time course was 9-12 times that generated after albumin infusion. In contrast the amounts of FPA generated after 200 IU/kg of the 4 high purity factor IX products were in all cases similar to albumin infusion. It was noted that some batches of high purity concentrates had short NAPTTs indicating that current in vitro tests for potential thrombogenicity may be misleading in predicting the effects of these concentrates in vivo.

A Comparison of the in Vitro and in Vivo Thrombogenic Activity of Factor IX Concentrates Using Stasis (Wessler) and Non-Stasis Rabbit Models

1980 ◽  
Vol 44 (02) ◽  
pp. 081-086 ◽  
Author(s):  
C V Prowse ◽  
A E Williams
Keyword(s):  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Factor Ix ◽  
Coagulation System ◽  
In Vitro Tests ◽  
Clinical Use ◽  
Low Activity

SummaryThe thrombogenic effects of selected factor IX concentrates were evaluated in two rabbit models; the Wessler stasis model and a novel non-stasis model. Concentrates active in either the NAPTT or TGt50 in vitro tests of potential thrombogenicity, or both, caused thrombus formation in the Wessler technique and activation of the coagulation system in the non-stasis model. A concentrate with low activity in both in vitro tests did not have thrombogenic effects in vivo, at the chosen dose. Results in the non-stasis model suggested that the thrombogenic effects of factor IX concentrates may occur by at least two mechanisms. A concentrate prepared from platelet-rich plasma and a pyrogenic concentrate were also tested and found to have no thrombogenic effect in vivo.These studies justify the use of the NAPTT and TGt50 in vitro tests for the screening of factor IX concentrates prior to clinical use.

Inhibition of Fibrinolysis and Fibrinogenolysis in Man: Comparison of ε-Aminocaproic Acid and Kallikrein Inhibitor

1963 ◽  
Vol 10 (01) ◽  
pp. 106-119 ◽  
Author(s):  
E Beck ◽  
R Schmutzler ◽  
F Duckert ◽  
Keyword(s):  
Aminocaproic Acid ◽  
Side Reactions ◽  
In Vitro Tests ◽  
Factor V ◽  
Clinical Use ◽  
Strong Inhibitor ◽  
Kallikrein Inhibitor ◽  
Therapeutic Possibilities

SummaryInhibitor of kallikrein and trypsin (KI) extracted from bovine parotis was compared with ε-aminocaproic acid (EACA): both substances inhibit fibrinolysis induced with streptokinase. EACA is a strong inhibitor of fibrinolysis in concentrations higher than 0, 1 mg per ml plasma. The same amount and higher concentrations are not able to inhibit completely the proteolytic-side reactions of fibrinolysis (fibrinogenolysis, diminution of factor V, rise of fibrin-polymerization-inhibitors). KI inhibits well proteolysis of plasma components in concentrations higher than 2,5 units per ml plasma. Much higher amounts of KI are needed to inhibit fibrinolysis as demonstrated by our in vivo and in vitro tests.Combination of the two substances for clinical use is suggested. Therapeutic possibilities are discussed.

Antioxidant Activity, Phenolic Content and Hematoprotective Effects of Cleome arabica Polyphenolic Leaf Extract

2019 ◽  
Author(s):  
C. Tigrine ◽  
A. Kameli
Keyword(s):  
Antioxidant Activity ◽  
Biological Effects ◽  
Reducing Power ◽  
Hematological Toxicity ◽  
Protective Effects ◽  
Ferrous Ions ◽  
Polyphenolic Extract ◽  
Cleome Arabica

In this study a polyphenolic extract from Cleome arabica leaves (CALE) was investigated for its antioxidant activity in vitro using DPPH•, metal chelating and reducing power methods and for its protective effects against AraC-induced hematological toxicity in vivo using Balb C mice. Results indicated that CALE exhibited a strong and dose-dependent scavenging activity against the DPPH• free radical (IC50 = 4.88 μg/ml) and a high reducing power activity (EC50 = 4.85 μg/ml). Furthermore, it showed a good chelating effects against ferrous ions (IC50 = 377.75 μg/ml). The analysis of blood showed that subcutaneous injection of AraC (50 mg/kg) to mice during three consecutive days caused a significant myelosupression (P < 0.05). The combination of CALE and AraC protected blood cells from a veritable toxicity. Where, the number of the red cells, the amount of hemoglobin and the percentage of the hematocrite were significantly high. On the other hand, AraC cause an elevation of body temperature (39 °C) in mice. However, the temperature of the group treated with CALE and AraC remained normal and did not exceed 37.5 °C. The observed biological effects of CALE, in vitro as well as in vivo, could be due to the high polyphenol and flavonoid contents. In addition, the antioxidant activity of CALE suggested to be responsible for its hematoprotective effect.

Influence of β-Cyclodextrin and Hydroxypropyl-β-Cyclodextrin on Enhancement of Solubility and Dissolution of Isradipine

2017 ◽  
Vol 10 (3) ◽  
pp. 3752-3757
Author(s):  
Narendar D ◽  
Ettireddy S
Keyword(s):  
Inclusion Complex ◽  
Dissolution Rate ◽  
Solid Dispersions ◽  
Physical Stability ◽  
Molecular Complexes ◽  
In Vitro Dissolution ◽  
Molar Ratio ◽  
Phase Solubility ◽  
Cyclodextrin Complexation

The content of this investigation was to study the influence of β-cyclodextrin and hydroxy propyl-β-cyclodextrin complexation on enhancement of solubility and dissolution rate of isradipine. Based on preliminary phase solubility studies, solid complexes prepared by freeze drying method in 1:1 molar ratio were selected and characterized by DSC for confirmation of complex formation. Prepared solid dispersions were evaluated for drug content, solubility and in vitro dissolution. The physical stability of optimized formulation was studied at refrigerated and room temperature for 2 months. Solid state characterization of optimized complex performed by DSC and XRD studies.  Dissolution rate of isradipine was increased compared with pure drug and more with HP-β-CD inclusion complex than β-CD. DSC and XRD analyzes that drug was in amorphous form, when the drug was incorporated as isradipine β-CD and HP-β-CD inclusion complex. Stability studies resulted in low or no variations in the percentage of complexation efficiency suggesting good stability of molecular complexes. The results conclusively demonstrated that the enhancement of solubility and dissolution rate of isradipine by drug-cyclodextrin complexation was achieved.   

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