Blood compatibility evaluations of two-dimensional Ti3C2Tx nanosheets

Author(s):  
Hongbo Yu ◽  
Yi Wan ◽  
Guiyin Zhang ◽  
Xiuhong Huang ◽  
Lichen Lin ◽  
...  

Abstract Two-dimensional (2D) nanomaterial Ti3C2Tx is a novel biomaterial used for medical apparatus. For its application, biosafety serves as a prerequisite for their use in vivo. So far, no research has systematically reported how Ti3C2Tx interacts with various components in the blood. In this work, we evaluated the hemocompatibility of Ti3C2Tx nanosheets which we prepared by HF etching. Effects of the concentration and size of Ti3C2Tx on the morphology and hemolysis rate of human red blood cells (RBCs), the structure and conformation of plasma proteins, the complement activation, as well as in vitro blood coagulation were studied. In general, Ti3C2Tx takes on good blood compatibility, but in the case of high concentration (>30 μg/mL) and “Small size” (about 100 nm), it led to the rupture of RBCs membrane and a higher rate of hemolysis. Meanwhile, platelets and complement were inclined to be activated with the increased concentration, accompanying the changed configuration of plasma proteins dependent on concentration. Surprisingly, the presence of Ti3C2Tx did not significantly disrupt the coagulation. In vitro cell culture, the results prove that when the Ti3C2Tx concentration is as high as 60μg/mL and still has good biological safety. By establishing a fuzzy mathematical model, it was proved that the hemocompatibility of Ti3C2Tx is more concentration-dependent than size-dependent, and the hemolysis rate is the most sensitive to the size and concentration of the Ti3C2Tx. These findings provide insight into the potential use of Ti3C2Tx as biofriendly nanocontainers for biomaterials in vivo.

1994 ◽  
Vol 49 (7-8) ◽  
pp. 483-488 ◽  
Author(s):  
Suzan Bandak ◽  
Martin Czejka ◽  
Johann Schüller

In this study, the in vitro interaction of epirubicin (EPR), a cytostatic antibiotic, with plasma proteins (PP), namely α-HSA, γ-HSG, α+β-HSG and with isolated human red blood cells (RBCs) was investigated and further correlated with the in vivo pharmacokinetics and binding of EPR and two of its metabolites, 13-dihydroepirubicin and 7-deoxydoxorubicinone to RBCs. The in vitro encapsulation rate in isolated erythrocytes amounts to 52.9 ± 2.8% and remains constant within the range of studied concentrations (2.5-20 μg/ml). EPR was found to bind differently to the various PP in vitro. Binding to α-HSA amounted up to 51.0 ± 7.10%, to α + β-HSG 79.45 ± 2.7%, to γ-HSG 57.1 ± 2.8%. The in vivo-binding rate of EPR, dihydroepirubicin and deoxydoxorubicinone to RBCs after 5 min of injection was 32 ± 6.96%, 11.6 ± 3.1% and 10.05 ± 3.5% respectively, their availability in serum was 42.6 ± 11.8%, 2.4 ± 0.4% and 1.2 ± 0.67% respectively


Author(s):  
U. Aebi ◽  
L.E. Buhle ◽  
W.E. Fowler

Many important supramolecular structures such as filaments, microtubules, virus capsids and certain membrane proteins and bacterial cell walls exist as ordered polymers or two-dimensional crystalline arrays in vivo. In several instances it has been possible to induce soluble proteins to form ordered polymers or two-dimensional crystalline arrays in vitro. In both cases a combination of electron microscopy of negatively stained specimens with analog or digital image processing techniques has proven extremely useful for elucidating the molecular and supramolecular organization of the constituent proteins. However from the reconstructed stain exclusion patterns it is often difficult to identify distinct stain excluding regions with specific protein subunits. To this end it has been demonstrated that in some cases this ambiguity can be resolved by a combination of stoichiometric labeling of the ordered structures with subunit-specific antibody fragments (e.g. Fab) and image processing of the electron micrographs recorded from labeled and unlabeled structures.


1969 ◽  
Vol 22 (03) ◽  
pp. 577-583 ◽  
Author(s):  
M.M.P Paulssen ◽  
A.C.M.G.B Wouterlood ◽  
H.L.M.A Scheffers

SummaryFactor VIII can be isolated from plasma proteins, including fibrinogen by chromatography on agarose. The best results were obtained with Sepharose 6B. Large scale preparation is also possible when cryoprecipitate is separated by chromatography. In most fractions containing factor VIII a turbidity is observed which may be due to the presence of chylomicrons.The purified factor VIII was active in vivo as well as in vitro.


Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1382
Author(s):  
Mina Martini ◽  
Iolanda Altomonte ◽  
Domenico Tricò ◽  
Riccardo Lapenta ◽  
Federica Salari

The increase of knowledge on the composition of donkey milk has revealed marked similarities to human milk, which led to a growing number of investigations focused on testing the potential effects of donkey milk in vitro and in vivo. This paper examines the scientific evidence regarding the beneficial effects of donkey milk on human health. Most clinical studies report a tolerability of donkey milk in 82.6–98.5% of infants with cow milk protein allergies. The average protein content of donkey milk is about 18 g/L. Caseins, which are main allergenic components of milk, are less represented compared to cow milk (56% of the total protein in donkey vs. 80% in cow milk). Donkey milk is well accepted by children due to its high concentration of lactose (about 60 g/L). Immunomodulatory properties have been reported in one study in humans and in several animal models. Donkey milk also seems to modulate the intestinal microbiota, enhance antioxidant defense mechanisms and detoxifying enzymes activities, reduce hyperglycemia and normalize dyslipidemia. Donkey milk has lower calorie and fat content compared with other milks used in human nutrition (fat ranges from 0.20% to 1.7%) and a more favourable fatty acid profile, being low in saturated fatty acids (3.02 g/L) and high in alpha-linolenic acid (about 7.25 g/100 g of fat). Until now, the beneficial properties of donkey milk have been mostly related to whey proteins, among which β-lactoglobulin is the most represented (6.06 g/L), followed by α-lactalbumin (about 2 g/L) and lysozyme (1.07 g/L). So far, the health functionality of donkey milk has been tested almost exclusively on animal models. Furthermore, in vitro studies have described inhibitory action against bacteria, viruses, and fungi. From the literature review emerges the need for new randomized clinical trials on humans to provide stronger evidence of the potential beneficial health effects of donkey milk, which could lead to new applications as an adjuvant in the treatment of cardiometabolic diseases, malnutrition, and aging.


Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 132
Author(s):  
Johanna Simon ◽  
Gabor Kuhn ◽  
Michael Fichter ◽  
Stephan Gehring ◽  
Katharina Landfester ◽  
...  

Understanding the behavior of nanoparticles upon contact with a physiological environment is of urgent need in order to improve their properties for a successful therapeutic application. Most commonly, the interaction of nanoparticles with plasma proteins are studied under in vitro conditions. However, this has been shown to not reflect the complex situation after in vivo administration. Therefore, here we focused on the investigation of magnetic nanoparticles with blood proteins under in vivo conditions. Importantly, we observed a radically different proteome in vivo in comparison to the in vitro situation underlining the significance of in vivo protein corona studies. Next to this, we found that the in vivo corona profile does not significantly change over time. To mimic the in vivo situation, we established an approach, which we termed “ex vivo” as it uses whole blood freshly prepared from an animal. Overall, we present a comprehensive analysis focusing on the interaction between nanoparticles and blood proteins under in vivo conditions and how to mimic this situation with our ex vivo approach. This knowledge is needed to characterize the true biological identity of nanoparticles.


1981 ◽  
Vol 49 (1) ◽  
pp. 33-49 ◽  
Author(s):  
R. Kuriyama ◽  
H. Kanatani

Centrioles from spermatozoa of the starfish, Asterina pectinifera, were isolated and partially purified by solubilization of chromatin followed by sucrose density-gradient centrifugation. The ultrastructure of the isolated centriolar complex was investigated in whole mount preparations by electron microscopy. The complex unit was composed of a pair of centrioles and a pericentriolar structure, which associated with the distal end of the distal centriole by 9 spoke-like satellites extending radially to a marginal ring. Each satellite bifurcated at a dense node forming 2 fan-like shapes with a periodic striated pattern. The tubular structure of the centrioles easily disintegrated, leaving the pericentriolar structure or axonemal microtubules intact. The distal centriole in a spermatozoon served as an initiating site for flagellar microtubule assembly; that is, a number of “9 + 2′ axonemal tubules were observed adhering just beneath the distal end of the basal body. In experiments in vitro, polymerization of microtubule proteins purified from porcine brain was initiated by the structure at the ends of both proximal and distal centrioles, but not from the satellites or the marginal ring. Also, few if any microtubules were formed from the sides of each centriole, even in the presence of a high concentration of exogenous tubulin. On the other hand, centrioles of spermatozoa, when they were in mature ooplasm, could initiate the formation of sperm asters by microtubules. Therefore, centrioles in spermatozoa seem to be able to initiate microtubules in a 2 ways. A possible explanation of the difference between the 2 types of microtubule organization in vivo, i.e. in the sperm cell itself and in the ooplasm, it discussed.


2021 ◽  
Vol 18 ◽  
Author(s):  
Subheet Kumar Jain ◽  
Neha Panchal ◽  
Amrinder Singh ◽  
Shubham Thakur ◽  
Navid Reza Shahtaghi ◽  
...  

Background: Diclofenac sodium (DS) injection is widely used in the management of acute or chronic pain and inflammatory diseases. It incorporates 20 % w/v Transcutol-P as a solubilizer to make the stable injectable formulation. However, the use of Transcutol-P in high concentration leads to adverse effects such as severe nephrotoxicity, etc. Some advancements resulted in the formulation of an aqueous based injectable but that too used benzyl alcohol reported to be toxic for human use. Objective: To develop an injectable self-micro emulsifying drug delivery system (SMEDDS) as a novel carrier of DS for prompt release with better safety and efficacy. Methods: A solubility study was performed with different surfactants and co-surfactants. The conventional stirring method was employed for the formulation of SMEDDS. Detailed in vitro characterization was done for different quality control parameters. In vivo studies were performed using Wistar rats for pharmacokinetic evaluation, toxicological analysis, and analgesic activity. Results: The optimized formulation exhibited good physical stability, ideal globule size (156±0.4 nm), quick release, better therapeutics, and safety, increase in LD50 (221.9 mg/kg) to that of the commercial counterpart (109.9 mg/kg). Further, pre-treatment with optimized formulation reduced the carrageenan-induced rat paw oedema by 88±1.2 % after 4 h, compared to 77±1.6 % inhibition with commercial DS formulation. Moreover, optimized formulation significantly (p<0.05) inhibited the pain sensation in the acetic-acid induced writhing test in mice compared to its commercial equivalent with a better pharmacokinetic profile. Conclusion: The above findings confirmed that liquid SMEDDS could be a successful carrier for the safe and effective delivery of DS


1980 ◽  
Vol 45 (2) ◽  
pp. 435 ◽  
Author(s):  
Milutin Drobac ◽  
Harry Rakowski ◽  
Brian W. Gilbert ◽  
Michael X. Glynn ◽  
Malcolm D. Silver

2012 ◽  
Vol 9 (77) ◽  
pp. 3288-3302 ◽  
Author(s):  
Neha Arya ◽  
Viren Sardana ◽  
Meera Saxena ◽  
Annapoorni Rangarajan ◽  
Dhirendra S. Katti

Owing to the reduced co-relationship between conventional flat Petri dish culture (two-dimensional) and the tumour microenvironment, there has been a shift towards three-dimensional culture systems that show an improved analogy to the same. In this work, an extracellular matrix (ECM)-mimicking three-dimensional scaffold based on chitosan and gelatin was fabricated and explored for its potential as a tumour model for lung cancer. It was demonstrated that the chitosan–gelatin (CG) scaffolds supported the formation of tumoroids that were similar to tumours grown in vivo for factors involved in tumour-cell–ECM interaction, invasion and metastasis, and response to anti-cancer drugs. On the other hand, the two-dimensional Petri dish surfaces did not demonstrate gene-expression profiles similar to tumours grown in vivo . Further, the three-dimensional CG scaffolds supported the formation of tumoroids, using other types of cancer cells such as breast, cervix and bone, indicating a possible wider potential for in vitro tumoroid generation. Overall, the results demonstrated that CG scaffolds can be an improved in vitro tool to study cancer progression and drug screening for solid tumours.


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