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Rapid Formation of Plasma Protein Corona Critically Affects Nanoparticle Pathophysiology
Published in Lajos P. Balogh, Nano-Enabled Medical Applications, 2020
Stefan Tenzer, Dominic Docter, Jörg Kuharev, Anna Musyanovych, Verena Fetz, Rouven Hecht, Florian Schlenk, Dagmar Fischer, Klytaimnistra Kiouptsi, Christoph Reinhardt, Katharina Landfester, Hansjörg Schild, Michael Maskos, Shirley K. Knauer, Roland H. Stauber
Plasma protein binding. Human plasma samples were obtained from the citrated blood of 15 healthy individuals (according to institutional bioethics approval), pooled, stored in liquid nitrogen and used for all experiments comprising proteomics as well as cell studies [15]. Nanoparticles in buffer-A [15] were incubated with a tenfold excess of human plasma for different time points, loaded onto a sucrose cushion (0.7 M in buffer-A) and centrifuged through the cushion to separate nanoparticle–protein complexes from plasma (20 min at 15,300g, 4◦C; Supplementary Fig. S2). Pellets were washed three times with buffer-A, and proteins eluted by adding polyacrylamide gel electrophoresis (PAGE)/LC-MS buffer as described previously [15].
β2-Agonists: Terbutaline, Albuterol, and Fenoterol GüNther Hochhaus and Helmut MöLlmann
Published in Hartmut Derendorf, Günther Hochhaus, Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
Hartmut Derendorf, Günther Hochhaus
The plasma protein binding has been determined for all three drugs. Albuterol shows the lowest protein binding (7%),5 while terbutaline (14 to 25%)29 and fenoterol (35 to 40%)34 exhibit more pronounced interaction with plasma proteins. Overall, the protein binding of the three drugs is rather low. Differences in the protein binding among individual patients will therefore be of little clinical significance, as slight differences in binding will hardly affect the free, unbound drug fraction, which is important for the pharmacodynamic effects.
Psychopharmacology EMIs
Published in Michael Reilly, Bangaru Raju, Extended Matching Items for the MRCPsych Part 1, 2018
Active transport.Bioavailability.Bioequivalence.Blood–brain barrier.Elimination half-life.First-order kinetics.First-pass effect.Plasma protein binding.Volume of distribution.Zero-order kinetics.
Design, synthesis, docking, MD simulations, and anti-proliferative evaluation of thieno[2,3-d]pyrimidine derivatives as new EGFR inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Eman A. Sobh, Mohammed A. Dahab, Eslam B. Elkaeed, Aisha A. Alsfouk, Ibrahim M. Ibrahim, Ahmed M. Metwaly, Ibrahim H. Eissa
Since the approval of a novel medicine is based on its pharmacokinetic assessment and its biological activity, it is important to explore the pharmacokinetic qualities of a new chemical early on in the drug discovery process to prevent delays in approval or retraction51. Using erlotinib as a reference molecule, the ADMET characteristics of the synthesised compounds were evaluated computationally using Discovery Studio 4.0 (Figure 16 and Table 7). Although most compounds were predicted to have bad levels of aqueous solubility (Sol. L), most of them expressed good levels of intestinal absorption (Abs. L). Most of the tested compounds were anticipated to have high or very high levels of BBB penetration levels. Regarding the cytochrome P4502D6 inhibitory effects, most compounds were predicted as non-inhibitors. The level of plasma protein binding (PPB. L) model predicts that most compounds were expected to bind plasma protein over 90%.
A ROS-response hyaluronic acid-coated/chitosan polymer prodrug for enhanced tumour targeting efficacy of SN38
Published in Journal of Drug Targeting, 2023
Jianpeng Qin, Meng Sun, Yanli Zhen, Ji Li, Dongkai Wang
There may be the possibility of being adsorbed by plasma proteins when circulating in vivo since the polymer prodrugs have a large surface area, thus affecting delivery efficiency within the organism. The relationship between total drug concentration in plasma and efficacy will only be good if the degree of plasma protein binding of the agent is constant [21]. The adsorption capacity of SN38 polymer prodrug with different concentrations of BSA was studied to explore the retention ability of SN38 polymer prodrug in vivo (Figure 3B). It is not difficult to see that the protein adsorption rate of CS-S-SN38 was significantly higher than that of HA@CS-S-SN38. The reason may be the residual amino group of CS after coupling with SN38 produced the attachment of BSA due to electrostatic attraction. Besides, the protein adsorption of CS polymer prodrug was effectively reduced due to the surface charge reversal caused by the HA coating, which can prolong the circulation time of the nano-delivery system in the blood.
In vitro hepatic metabolism of the natural product quebecol
Published in Xenobiotica, 2023
We performed nonlinear least squares regression analysis in a plot containing the kdep values and the quebecol concentrations fitted to Equation 1 resulting in a biphasic plot as shown in Figure 7 which yielded values for KM (5.1 μM) and kdep([S]→0) (0.02160 min−1). The in vitro CLint values of quebecol glucuronidation were adjusted for any non-specific binding in microsomes using ultrafiltration with quebecol concentration at 15 μM. The in vitro unbound intrinsic clearance, CLint,u, microsomal fu,(mic), and other kinetics parameters were determined, and we reported these in Table 1. Additionally, to predict the clearance in human plasma, CLp, we determined the plasma protein binding in human plasma for quebecol using ultrafiltration.