scholarly journals Characterization of PCL and Chitosan Nanoparticles as Carriers of Enoxaparin and Its Antithrombotic Effect in Animal Models of Venous Thrombosis

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Lucas Bessa Prado ◽  
Stephany Cares Huber ◽  
Aline Barnabé ◽  
Fernanda Dutra Santiago Bassora ◽  
Devanira Souza Paixão ◽  
...  
Keyword(s):  
Oral Administration ◽  
Encapsulation Efficiency ◽  
Anticoagulant Activity ◽  
Chitosan Nanoparticles ◽  
Subcutaneous Administration ◽  
Double Emulsion ◽  
In Vivo Studies ◽  
Control Group ◽  
Antithrombotic Effect

This study was based on the preparation, characterization, and animal in vivo experiments performed to evaluate nanoparticles of poly(ɛ-caprolactone) (PCL) and chitosan as carriers of enoxaparin. The nanoparticles were characterized and presented satisfactory results in terms of size, polydispersity, and encapsulation efficiency. Anticoagulant activity of the nanoparticles was maintained for 14 hours when the administration was subcutaneous; however no activity was observed after oral administration. There was a significant reduction in thrombus size, in vivo, for both free and encapsulated enoxaparin in comparison with the control group after subcutaneous administration. Oral administration results however were indifferent. In conclusion, the double emulsion method w/o/w was efficient for enoxaparin encapsulation, producing spherical nanoparticles with high encapsulation efficiency. For in vivo studies, the encapsulated enoxaparin showed a sustained anticoagulant activity for a higher period of time compared to free enoxaparin, with an antithrombotic effect when administered subcutaneously.

Prevention of thrombosis following deep arterial injury in rats by bovine activated protein C requiring co-administration of bovine protein S

2003 ◽  
Vol 90 (08) ◽  
pp. 227-234 ◽  
Author(s):  
Björn Dahlbäck ◽  
Björn Arnljots ◽  
Karl Malm
Keyword(s):  
Protein C ◽  
Anticoagulant Activity ◽  
Activated Protein C ◽  
Protein S ◽  
Arterial Injury ◽  
Control Group ◽  
Clotting Time ◽  
Antithrombotic Effect

SummaryThe antithrombotic effect of bovine activated protein C (bAPC) given with or without bovine protein S (bPS) was investigated in a rat model of deep arterial injury. A segment of the left common carotid artery was isolated between vascular clamps and opened longitudinally. An endarterectomy was performed and the arteriotomy was closed with a running suture, whereafter the vessel was reperfused by removing the clamps. The antithrombotic effect (vascular patency rates 31 minutes after reperfusion) and the arteriotomy bleeding were measured. Ten treatment groups each containing 10 rats and a control group of 20 animals were in a blind random fashion given intravenous bolus injections of increasing doses of activated protein C, with or without co-administration of protein S. The groups received either bAPC alone (0.8, 0.4, 0.2 or 0.1 mg/kg), bAPC (0.8, 0.4, 0.2, 0.1 or 0.05 mg/kg) combined with bPS (0.6 mg/kg), or bPS alone (0.6 mg/kg) whereas the control group received vehicle only. Administered alone, bAPC or bPS had no antithrombotic effect, regardless of dosage. In contrast, all groups that were treated with bAPC in combination with bPS demonstrated a significant antithrombotic effect, as compared to controls. Neither bAPC, bPS, nor the combination of bAPC and bPS increased the arteriotomy bleeding significantly compared to controls. In vitro clotting assays using bAPC or bPS alone yielded only minor prolongation of clotting time, whereas bAPC combined with bPS prolonged the clotting time considerably, demonstrating the dependence on the APC-cofactor activity of bPS for expression of anticoagulant activity by bAPC. In conclusion, our study shows the in vivo significance of protein S as a cofactor to activated protein C, and that potent anti-thrombotic effect can be achieved by low doses of bAPC combined with bPS, without producing hemorrhagic side effects.

scholarly journals Topiramate is more effective than acetazolamide at lowering intracranial pressure

Cephalalgia ◽  
2018 ◽  
Vol 39 (2) ◽  
pp. 209-218 ◽  
Author(s):  
William J Scotton ◽  
Hannah F Botfield ◽  
Connar SJ Westgate ◽  
James L Mitchell ◽  
Andreas Yiangou ◽  
...  
Keyword(s):  
Intracranial Pressure ◽  
Oral Administration ◽  
Intracranial Hypertension ◽  
Idiopathic Intracranial Hypertension ◽  
Subcutaneous Administration ◽  
Female Rats ◽  
In Vivo Studies ◽  
Human Dose ◽  
High Doses

Background The management of idiopathic intracranial hypertension focuses on reducing intracranial pressure to preserve vision and reduce headaches. There is sparse evidence to support the use of some of the drugs commonly used to manage idiopathic intracranial hypertension, therefore we propose to evaluate the efficacy of these drugs at lowering intracranial pressure in healthy rats. Methods We measured intracranial pressure in female rats before and after subcutaneous administration of acetazolamide, topiramate, furosemide, amiloride and octreotide at clinical doses (equivalent to a single human dose) and high doses (equivalent to a human daily dose). In addition, we measured intracranial pressure after oral administration of acetazolamide and topiramate. Results At clinical and high doses, subcutaneous administration of topiramate lowered intracranial pressure by 32% ( p = 0.0009) and 21% ( p = 0.015) respectively. There was no significant reduction in intracranial pressure noted with acetazolamide, furosemide, amiloride or octreotide at any dose. Oral administration of topiramate significantly lowered intracranial pressure by 22% ( p = 0.018), compared to 5% reduction with acetazolamide ( p = >0.999). Conclusion Our in vivo studies demonstrated that both subcutaneous and oral administration of topiramate significantly lowers intracranial pressure. Other drugs tested, including acetazolamide, did not significantly reduce intracranial pressure. Future clinical trials evaluating the efficacy and side effects of topiramate in idiopathic intracranial hypertension patients would be of interest.

Oral Administration of Fucosylated Chondroitin Sulfate Oligomers in Gastro-Resistant Microcapsules Exhibits a Safe Antithrombotic Activity

2020 ◽  
Author(s):  
Lufeng Yan ◽  
Mengshan Zhu ◽  
Danli Wang ◽  
Wenyang Tao ◽  
Donghong Liu ◽  
...  
Keyword(s):  
Oral Administration ◽  
Chondroitin Sulfate ◽  
Anticoagulant Activity ◽  
Subcutaneous Administration ◽  
Selective Inhibition ◽  
Antithrombotic Effect ◽  
Antithrombotic Activity ◽  
Antithrombotic Effects ◽  
Dose Dependent ◽  
Coagulation Pathway

AbstractFucosylated chondroitin sulfate (FCS) polysaccharide isolated from sea cucumber has potent anticoagulant activity. Based on its resistance to the enzymes present in vertebrates, it may serve as an anticoagulant and shows antithrombotic effects when delivered through gastro-resistant (GR) tablets. However, due to the multiple plasma targets of FCS polysaccharide in the coagulation pathway, bleeding can occur after its oral administration. In the current study, we used FCS oligomers, in particular a mixture of oligosaccharides having 6 to 18 saccharide units, as the active ingredient in GR microcapsules for oral anticoagulation. In a Caco-2 model, the FCS oligomers showed higher absorption than native FCS polysaccharides. Oral administration of FCS oligomer-GR microcapsules provided a dose-dependent, prolonged anticoagulant effect with a selective inhibition of the intrinsic coagulation pathway when compared with subcutaneous administration of FCS oligomers or oral administration of unformulated FCS oligomers or native FCS-GR microspheres. Continued oral administration of FCS oligomer-GR microcapsules did not result in the accumulation of oligosaccharides in the plasma. Venous thrombosis animal models demonstrated that FCS oligomers delivered via GR microcapsules produced a potent antithrombotic effect dependent on their anticoagulant properties in the plasma, while oral administration of unformulated FCS oligomers at the same dose exhibited a weaker antithrombotic effect than the formulated version. Oral administration of FCS oligomer-GR microcapsules resulted in no bleeding, while oral administration of native FCS-GR microcapsules resulted in bleeding (p < 0.05). Our present results suggest that a FCS oligomer-GR microcapsule formulation represents an effective and safe oral anticoagulant for potential clinical applications.

scholarly journals Optimizing Manufacturing and Osseointegration of Ti6Al4V Implants through Precision Casting and Calcium and Phosphorus Ion Implantation? In Vivo Results of a Large-Scale Animal Trial

Materials ◽  
2020 ◽  
Vol 13 (7) ◽  
pp. 1670 ◽  
Author(s):  
Wölfle-Roos JV ◽  
Katmer Amet B ◽  
Fiedler J ◽  
Michels H ◽  
Kappelt G ◽  
...  
Keyword(s):  
Ion Implantation ◽  
Large Scale ◽  
In Vivo Studies ◽  
Control Group ◽  
Implant Surface ◽  
Precision Casting ◽  
Pull Out ◽  
Significant Difference ◽  
Calcium And Phosphorus

Background: Uncemented implants are still associated with several major challenges, especially with regard to their manufacturing and their osseointegration. In this study, a novel manufacturing technique—an optimized form of precision casting—and a novel surface modification to promote osseointegration—calcium and phosphorus ion implantation into the implant surface—were tested in vivo. Methods: Cylindrical Ti6Al4V implants were inserted bilaterally into the tibia of 110 rats. We compared two generations of cast Ti6Al4V implants (CAST 1st GEN, n = 22, and CAST 2nd GEN, n = 22) as well as cast 2nd GEN Ti6Al4V implants with calcium (CAST + CA, n = 22) and phosphorus (CAST + P, n = 22) ion implantation to standard machined Ti6Al4V implants (control, n = 22). After 4 and 12 weeks, maximal pull-out force and bone-to-implant contact rate (BIC) were measured and compared between all five groups. Results: There was no significant difference between all five groups after 4 weeks or 12 weeks with regard to pull-out force (p > 0.05, Kruskal Wallis test). Histomorphometric analysis showed no significant difference of BIC after 4 weeks (p > 0.05, Kruskal–Wallis test), whereas there was a trend towards a higher BIC in the CAST + P group (54.8% ± 15.2%), especially compared to the control group (38.6% ± 12.8%) after 12 weeks (p = 0.053, Kruskal–Wallis test). Conclusion: In this study, we found no indication of inferiority of Ti6Al4V implants cast with the optimized centrifugal precision casting technique of the second generation compared to standard Ti6Al4V implants. As the employed manufacturing process holds considerable economic potential, mainly due to a significantly decreased material demand per implant by casting near net-shape instead of milling away most of the starting ingot, its application in manufacturing uncemented implants seems promising. However, no significant advantages of calcium or phosphorus ion implantation could be observed in this study. Due to the promising results of ion implantation in previous in vitro and in vivo studies, further in vivo studies with different ion implantation conditions should be considered.

scholarly journals Nanoparticle Delivered Anti-miR-141-3p for Stroke Therapy

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1011
Author(s):  
Karishma Dhuri ◽  
Rutesh N. Vyas ◽  
Leslie Blumenfeld ◽  
Rajkumar Verma ◽  
Raman Bahal
Keyword(s):  
Ischemic Stroke ◽  
Nucleic Acid ◽  
Double Emulsion ◽  
Artery Occlusion ◽  
Brain Parenchyma ◽  
Confocal Imaging ◽  
In Vivo Studies ◽  
Stroke Therapy ◽  
Systemic Delivery

Ischemic stroke and factors modifying ischemic stroke responses, such as social isolation, contribute to long-term disability worldwide. Several studies demonstrated that the aberrant levels of microRNAs contribute to ischemic stroke injury. In prior studies, we established that miR-141-3p increases after ischemic stroke and post-stroke isolation. Herein, we explored two different anti-miR oligonucleotides; peptide nucleic acid (PNAs) and phosphorothioates (PS) for ischemic stroke therapy. We used US FDA approved biocompatible poly (lactic-co-glycolic acid) (PLGA)-based nanoparticle formulations for delivery. The PNA and PS anti-miRs were encapsulated in PLGA nanoparticles by double emulsion solvent evaporation technique. All the formulated nanoparticles showed uniform morphology, size, distribution, and surface charge density. Nanoparticles also exhibited a controlled nucleic acid release profile for 48 h. Further, we performed in vivo studies in the mouse model of ischemic stroke. Ischemic stroke was induced by transient (60 min) occlusion of middle cerebral artery occlusion followed by a reperfusion for 48 or 72 h. We assessed the blood-brain barrier permeability of PLGA NPs containing fluorophore (TAMRA) anti-miR probe after systemic delivery. Confocal imaging shows uptake of fluorophore tagged anti-miR in the brain parenchyma. Next, we evaluated the therapeutic efficacy after systemic delivery of nanoparticles containing PNA and PS anti-miR-141-3p in mice after stroke. Post-treatment differentially reduced both miR-141-3p levels in brain tissue and infarct injury. We noted PNA-based anti-miR showed superior efficacy compared to PS-based anti-miR. Herein, we successfully established that nanoparticles encapsulating PNA or PS-based anti-miRs-141-3p probes could be used as a potential treatment for ischemic stroke.

scholarly journals Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 386
Author(s):  
Tung-Hu Tsai ◽  
Yu-Jen Chen ◽  
Li-Ying Wang ◽  
Chen-Hsi Hsieh
Keyword(s):  
Stereotactic Body Radiation Therapy ◽  
In Vivo Studies ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Hep G2 ◽  
Time Curve ◽  
Dose Dependent

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).

Evaluation of Annona muricata (Graviola) leaves activity against experimental trichinellosis: in vitro and in vivo studies

2021 ◽  
Vol 95 ◽  
Author(s):  
E.S. El-Wakil ◽  
H.F. Abdelmaksoud ◽  
T.S. AbouShousha ◽  
M.M.I. Ghallab
Keyword(s):  
Culture Media ◽  
Trichinella Spiralis ◽  
Drug Effects ◽  
In Vivo Studies ◽  
Control Group ◽  
Annona Muricata ◽  
Group I ◽  
Small Intestinal

Abstract Our work aimed to evaluate the possible effect of Annona muricata (Graviola) leaf extract on Trichinella spiralis in in vitro and in vivo studies. Trichinella spiralis worms were isolated from infected mice and transferred to three culture media – group I (with no drugs), group II (contained Graviola) and group III (contained albendazole) – then they were examined using the electron microscope. In the in vivo study, mice were divided into five groups: GI (infected untreated), GII (prophylactically treated with Graviola for seven days before infection), GIII (infected and treated with Graviola), GIV (infected and treated with albendazole) and GV (infected and treated with a combination of Graviola plus albendazole in half doses). Drug effects were assessed by adults and larvae load beside the histopathological small intestinal and muscular changes. A significant reduction of adult and larval counts occurred in treated groups in comparison to the control group. Histopathologically, marked improvement in the small intestinal and muscular changes was observed in treated groups. Also, massive destruction of the cultured adults’ cuticle was detected in both drugs. This study revealed that Graviola leaves have potential activity against trichinellosis, especially in combination with albendazole, and could serve as an adjuvant to anti-trichinellosis drug therapy.

scholarly journals Design and Characterization of Combinational Domperidone-Famotidine Floating Drug Delivery System - In vitro and In vivo studies

2021 ◽  
Vol 62 (2) ◽  
pp. 144-162
Author(s):  
Mounika Chidurala ◽  
Raveendra Reddy J
Keyword(s):  
Drug Release ◽  
Oral Administration ◽  
Quality By Design ◽  
Release Kinetics ◽  
Cost Effective ◽  
Fickian Diffusion ◽  
In Vivo Studies ◽  
Pharmacokinetic Studies

Introduction: The drawbacks assosiated with oral administration of drugscan be controlled or minimized by gastro retentive formulations that remain buoyant within the stomach for an extended time by providing prolonged gastric retention and releasethe drug in an exceedingly extended manner thereby improving bioavailability. The current research was to develop and optimize Domperidone and Famotidine floating tablets with extended release by Quality by Design approach. Method: Based on QTPP (Quality Target Product Profile), CQAs (Critical Quality Attributes)wereidentified. Risk analysis by the evaluation of formulation and process parameters showed that optimizing the levels of polymers could reduce high risk to achieve the target profile. A 23factor experimental design with midpoints was selected for statistical analysis and optimization. Results: HPMC K100 and Carbopol 934P had a positive effect while ethyl cellulose demonstrated a negative effect on the selected responses. Drug release kinetics followed the first-order release with Higuchi diffusion and Fickian diffusion. Optimized formula satisfying all the required parameters was selected and evaluated. The predicted response values were in close agreement with experimental response values. Abdominal X-ray imaging after oral administration of the tablets on a healthy rabbit’s stomach confirmed the extended floating behavior with shorter lag time. In vivo, pharmacokinetic studies in rabbits revealed that the optimized formulation exhibited prolonged drug release with enhanced Cmax, tmax, AUCo-t, and t1/2 of an optimized product when compared to the marketed product. Conclusions: It has been concluded that the application of Quality by Design in the formulation and optimization reduced the number of trials to produce a cost-effective formula.

HERBAL CREAMS OF REISHI EXTRACT AND TEA TREE OIL FOR HIRSUTISM–AN IN VIVO STUDY

2020 ◽  
pp. 106-110
Author(s):  
SANGEETA CHOUDHURY ◽  
BLR MADHAVI
Keyword(s):  
Topical Application ◽  
Hair Growth ◽  
Ethanolic Extract ◽  
Hair Follicles ◽  
In Vivo Studies ◽  
Control Group ◽  
Tea Tree Oil ◽  
Tea Tree

Objective: The aim of this work to formulate, evaluate and compare the effectiveness of herbal creams containing extract of reishi and tea tree oil for treating hirsutism. Methods: Herbal ingredients were authenticated. Cream base was initially formulated. Three formulations of herbal cream were prepared. Reishi ethanolic extract, tea tree oil, and combination of tea tree oil and reishi extract were added to the cream base and formulated cream were named as RHC, THC and RTC respectively. In vitro evaluations on herbal creams were done for the physicochemical characteristics. In vivo studies were carried out on female Swiss Albino mice for the activity against hair growth by topical application of cream to shaved skin. The histological and morphometric evaluation was carried out. Skin irritancy study was conducted. Results: The herbal creams showed desirable physicochemical properties like pH, viscosity and spreadability. Statistical analysis for the length of hair was performed by using one way ANOVA followed by DUNNET’S post hoc test where THC and RTC were found to be significant whereas RHC showed no significant reduction of hair growth compared to control. RTC showed a significant effect at p<0.05 and hair growth reduction was significant for THC at p<0.001 compared to the control group. RTC and THC showed mild to moderate reduction in the size of the hair follicles with a reduction of sebaceous gland size in the histological analysis. Conclusion: Topical application of herbal creams to mice showed that hair growth was fastest in group RHC and was slowest in group THC and intermediate with RTC. It can be concluded that these herbal actives can be used as an effective treatment against hirsutism. Within the study period, tea tree oil was found to be more effective than reishi extract and the combination product. Further formulation studies and in vivo studies need to be carried out on reishi to assess its effectiveness against hirsutism.

scholarly journals A Comprehensive Toxicological Assessment of Fulvic Acid

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Chongshan Dai ◽  
Xilong Xiao ◽  
Yonglei Yuan ◽  
Gaurav Sharma ◽  
Shusheng Tang
Keyword(s):  
Oral Administration ◽  
Fulvic Acid ◽  
Clinical Chemistry ◽  
Clinical Signs ◽  
Micronucleus Assay ◽  
The Body ◽  
Feed Consumption ◽  
Control Group ◽  
Toxicological Studies

Fulvic acid (FA), a humic substance, has several nutraceutical properties, including anti-inflammation, antimicrobial, and immune regulation abilities. However, systematic safety assessment remains insufficient. In the present study, a battery of toxicological studies was conducted per internationally accepted standards to investigate the genotoxicity and repeated-dose oral toxicity of FA. Sprague-Dawley (SD) rats or ICR mice were used. Compared to the control group, there were no significant changes (all p > 0.05 ) in all FA treatment groups in the bacterial reverse mutation test, in vitro mammalian chromosome aberration test, in vivo sperm shape abnormality assay, and in vivo mouse micronucleus assay. The acute toxicity test showed that no mortality or toxic effect was observed following oral administration of the maximum dose of 5,000 mg/kg BW/day to mice or rats. A 60-day subchronic study was conducted at 0 (control), 200, 1,000, and 5,000 mg/kg/day. Compared to the control group, there were no significant changes (all p > 0.05 ) in the body weights, feed consumption, clinical signs, hematology, clinical chemistry, organ weights, or histopathology examinations. In conclusion, the no-observed-adverse-effect-level (NOAEL) of FA supplementation from the 60-day study was determined to be 5,000 mg/kg body weight/day, the highest dose tested. Our findings suggest that the oral administration of FA may have higher safety.

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