scholarly journals Distinct Proteins in Protein Corona of Nanoparticles Represent a Promising Venue for Endogenous Targeting – Part II: In vitro and in vivo Kinetics Study

2020 ◽  
Vol Volume 15 ◽  
pp. 9539-9556
Author(s):  
Aya Ahmed Sebak ◽  
Iman Emam Omar Gomaa ◽  
Aliaa Nabil ElMeshad ◽  
Mahmoud Hussien Farag ◽  
Ulrike Breitinger ◽  
...  
Keyword(s):  
Protein Corona ◽  
Kinetics Study ◽  
In Vivo Kinetics

scholarly journals Inside Front Cover: Species Differences in in vitro and Estimated in vivo Kinetics for Intestinal Microbiota Mediated Metabolism of Acetyl‐deoxynivalenols

2021 ◽  
Vol 65 (9) ◽  
pp. 2170020
Author(s):  
Jing Jin ◽  
Albertus Spenkelink ◽  
Karsten Beekmann ◽  
Marta Baccaro ◽  
Fuguo Xing ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Species Differences ◽  
Front Cover ◽  
In Vivo Kinetics

scholarly journals Unraveling the In Vivo Protein Corona

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 132
Author(s):  
Johanna Simon ◽  
Gabor Kuhn ◽  
Michael Fichter ◽  
Stephan Gehring ◽  
Katharina Landfester ◽  
...  
Keyword(s):  
Plasma Proteins ◽  
Ex Vivo ◽  
Protein Corona ◽  
Blood Proteins ◽  
Therapeutic Application ◽  
Complex Situation ◽  
Ex Vivo Approach ◽  
In Vivo Administration

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.

scholarly journals An In Vitro–In Vivo Simulation Approach for the Prediction of Bioequivalence

Materials ◽  
2021 ◽  
Vol 14 (3) ◽  
pp. 555
Author(s):  
Marilena Vlachou ◽  
Vangelis Karalis
Keyword(s):  
Mathematical Description ◽  
Development Process ◽  
Bioequivalence Study ◽  
In Vitro Dissolution ◽  
Monte Carlo Techniques ◽  
In Vivo Kinetics ◽  
Probability Of Success ◽  
Made In

The aim of this study was to develop a new in vitro–in vivo simulation (IVIVS) approach in order to predict the outcome of a bioequivalence study. The predictability of the IVIVS procedure was evaluated through its application in the development process of a new generic product of amlodipine/irbesartan/hydrochlorothiazide. The developed IVIVS methodology is composed of three parts: (a) mathematical description of in vitro dissolution profiles, (b) mathematical description of in vivo kinetics, and (c) development of joint in vitro–in vivo simulations. The entire programming was done in MATLAB® and all created scripts were validated through other software. The IVIVS approach can be implemented for any number of subjects, clinical design, variability and can be repeated for thousands of times using Monte Carlo techniques. The probability of success of each scenario is recorded and finally, an overall assessment is made in order to select the most suitable batch. Alternatively, if the IVIVS shows reduced probability of BE success, the R&D department is advised to reformulate the product. In this study, the IVIVS approach predicted successfully the BE outcome of the three drugs. During the development of generics, the IVIVS approach can save time and expenses.

scholarly journals Supervised Learning Model Predicts Protein Adsorption to Nanotubes

2021 ◽  
Author(s):  
Rebecca L Pinals ◽  
Nicholas Ouassil ◽  
Jackson Travis Del Bonis-O'Donnell ◽  
Jeffrey W Wang ◽  
Markita P Landry
Keyword(s):  
Amino Acids ◽  
Protein Adsorption ◽  
Biological Systems ◽  
Protein Corona ◽  
Engineered Nanoparticles ◽  
Mass Spectrometry Data ◽  
In Vitro Synthesis ◽  
Intractable Problem

Engineered nanoparticles are advantageous for numerous biotechnology applications, including biomolecular sensing and delivery. However, testing the compatibility and function of nanotechnologies in biological systems requires a heuristic approach, where unpredictable biofouling often prevents effective implementation. Such biofouling is the result of spontaneous protein adsorption to the nanoparticle surface, forming the "protein corona" and altering the physicochemical properties, and thus intended function, of the nanotechnology. To better apply engineered nanoparticles in biological systems, herein, we develop a random forest classifier (RFC) trained with proteomic mass spectrometry data that identifies which proteins adsorb to nanoparticles. We model proteins that populate the corona of a single-walled carbon nanotube (SWCNT)-based optical nanosensor. We optimize the classifier and characterize the classifier performance against other models. To evaluate the predictive power of our model, we then apply the classifier to rapidly identify and experimentally validate proteins with high binding affinity to SWCNTs. Using protein properties based solely on amino acid sequence, we further determine protein features associated with increased likelihood of SWCNT binding: proteins with high content of solvent-exposed glycine residues and non-secondary structure-associated amino acids. Furthermore, proteins with high leucine residue content and beta-sheet-associated amino acids are less likely to form the SWCNT protein corona. The classifier presented herein provides an important tool to undertake the otherwise intractable problem of predicting protein-nanoparticle interactions, which is needed for more rapid and effective translation of nanobiotechnologies from in vitro synthesis to in vivo use.

scholarly journals The fate of a designed protein corona on nanoparticles in vitro and in vivo

2015 ◽  
Vol 6 ◽  
pp. 36-46 ◽  
Author(s):  
Denise Bargheer ◽  
Julius Nielsen ◽  
Gabriella Gébel ◽  
Markus Heine ◽  
Sunhild C Salmen ◽  
...  
Keyword(s):  
Superparamagnetic Iron Oxide ◽  
Protein Corona ◽  
Blood Stream ◽  
Minor Importance ◽  
Iron Oxide Particles ◽  
Corona Formation ◽  
The Stability ◽  
Covalently Bound

A variety of monodisperse superparamagnetic iron oxide particles (SPIOs) was designed in which the surface was modified by PEGylation with mono- or bifunctional poly(ethylene oxide)amines (PEG). Using 125I-labeled test proteins (transferrin, albumin), the binding and exchange of corona proteins was studied first in vitro. Incubation with 125I-transferrin showed that with increasing grade of PEGylation the binding was substantially diminished without a difference between simply adsorbed and covalently bound protein. However, after incubation with excess albumin and subsequently whole plasma, transferrin from the preformed transferrin corona was more and more lost from SPIOs in the case of adsorbed proteins. If non-labeled transferrin was used as preformed corona and excess 125I-labeled albumin was added to the reaction mixtures with different SPIOs, a substantial amount of label was bound to the particles with initially adsorbed transferrin but little or even zero with covalently bound transferrin. These in vitro experiments show a clear difference in the stability of a preformed hard corona with adsorbed or covalently bound protein. This difference seems, however, to be of minor importance in vivo when polymer-coated 59Fe-SPIOs with adsorbed or covalently bound 125I-labeled mouse transferrin were injected intravenously in mice. With both protein coronae the 59Fe/125I-labelled particles were cleared from the blood stream within 30 min and appeared in the liver and spleen to a large extent (>90%). In addition, after 2 h already half of the 125I-labeled transferrin from both nanodevices was recycled back into the plasma and into tissue. This study confirms that adsorbed transferrin from a preformed protein corona is efficiently taken up by cells. It is also highlighted that a radiolabelling technique described in this study may be of value to investigate the role of protein corona formation in vivo for the respective nanoparticle uptake.

Cell Kinetics Study of Upper Aerodigestive Tract Squamous Cell Carcinoma Using Bromodeoxyuridine

1993 ◽  
Vol 102 (1) ◽  
pp. 42-46 ◽  
Author(s):  
Toshikazu Hirano ◽  
Robert P. Zitsch ◽  
Jack L. Gluckman
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Kinetics ◽  
Aerodigestive Tract ◽  
In Vitro Test ◽  
Kinetics Study ◽  
Upper Aerodigestive Tract

Thirty patients treated for squamous cell carcinoma of the upper aerodigestive tract were reviewed for a cell kinetics study using bromodeoxyuridine (BrdU). Fresh specimens were obtained from the primary site of the tumors and incubated in Dulbecco's modified Eagle's medium containing BrdU to label S-phase tumor cells. The tumor specimens were stained immunohistochemically with monoclonal antibody against BrdU. The results demonstrated that the BrdU labeling index (BrdU LI) in these cases (470.3 ± 118.2) was greater than the BrdU LI in normal mucosa (162 ± 52.4). In a comparison of the clinical data and histopathologic features, the BrdU LI showed an inverse correlation with patient age (r = −.558; p < .01) and a direct correlation with the frequency of mitoses (r = .411; p < .05). Although the significance of the BrdU LI as a prognostic factor cannot be determined at present, this technique provides a simple in vitro test that avoids the potential hazards of in vivo labeling or the use of radioactive materials.

The fate of a designed protein corona on nanoparticles in vitro and in vivo

nano Online ◽  
2016 ◽  
Author(s):  
Denise Bargheer ◽  
Julius Nielsen ◽  
Gabriella Gébel ◽  
Markus Heine ◽  
Salmen ◽  
...  
Keyword(s):  
Protein Corona
Sign in / Sign up

Export Citation Format

Share Document