Modeling Of Uptake Kinetics Research Articles

Modeling of magnetoliposome uptake in human pancreatic tumor cells in vitro

The internalization kinetics resulting from magnetic nanoparticle interactions with tumor cells play an important role in nanoparticle-based cancer treatment efficiency. Here, the uptake kinetics of magnetoliposomes (ML) into human pancreatic tumor cells (MiaPaCa-2 and BxPC-3) are quantified using magnetic particle spectrometry. A comparison to the uptake kinetics for healthy L929 cells is given. The experimental results are used for the development of an uptake kinetics model describing the three relevant internalization processes: ML adsorption to the cell membrane, endo- and exocytosis. By fitting of experimental data, the rate constant of each internalization process is determined enabling the prediction of internalized ML at any incubation time. After seven hours incubation time, MiaPaCa-2 internalized three times more ML than BxPC-3 and L929 cells even though their ML adsorption rate constants were nearly the same. As the interaction of the ML with the cell membrane is non-specific, the uptake kinetics mirror the individual cell response to ML internalization. With a new mathematical term to cover the exocytosis contribution to the overall internalization process, the extended uptake kinetics model offers new possibilities to analyze the specific internalization mechanism for other nanoparticle and cell types.

The effect of growth rate on uranium partitioning between individual calcite crystals and fluid

Elemental to calcium ratios in calcium carbonate minerals are used to study environmental conditions. In particular, uranium to calcium ratio (U/Ca) has been proposed as a proxy for seawater carbonate ion concentration (CO32−) and seawater pH. This work is focused on the evaluation of growth rate and its effect on uranium partitioning between calcite and fluid. We grew inorganic calcite (by diffusion of CO2) isothermally from NH4Cl-CaCl2 doped with uranium. The growth rate of calcite (crystal extension rate, V) was monitored by sequentially spiking calcite-precipitating fluids with rare earth element (REE) dopants. The REE was analyzed with secondary ion mass spectrometry (SIMS) at spots matching those where U/Ca was determined. Partition coefficient KU=(U/Ca)calcite/(U/Ca)fluid increases with increasing growth rate (V). Specifically, KU increases from 0.02 to 0.06 when V increases from 0.01 to 0.14nm/s and remains nearly constant at faster rates. Numerical simulations using the growth entrapment model (GEM) and unified uptake kinetics model (UUKM) were undertaken to explain KU-V relationship in the recent data on calcite.

Facile synthesis of 55Fe-labeled well-dispersible hematite nanoparticles for bioaccumulation studies in nanotoxicology

Although water-dispersible engineered nanoparticles (ENPs) have a wide range of applications, the ENPs used in many nanotoxicological studies tend to form micron-sized aggregates in the exposure media and thus cannot reflect the toxicity of real nanoparticles. Here we described the synthesis of bare hematite nanoparticles (HNPs-0) and two poly(acrylic acid) (PAA)-coated forms (HNPs-1 and HNPs-2). All three HNPs were well dispersed in deionized water, but HNPs-0 quickly aggregated in the three culture media tested. By contrast, the suspensions of HNPs-1 and HNPs-2 remained stable, with negligible amounts of PAA and Fe3+ liberated from either one under the investigated conditions. To better quantify the accumulation of the coated HNPs, a relatively innocuous 55Fe-labeled form of HNPs-2 was synthesized as an example and its accumulation in three phytoplankton species was tested. Consistent with the uptake kinetics model for conventional pollutants, the cellular accumulation of HNPs-2 increased linearly with exposure time for two of the three phytoplankton species. These results demonstrate the utility of 55Fe-labeled well-dispersible HNPs as a model material for nanoparticle bioaccumulation studies in nanotoxicology.

A unified approach to model uptake kinetics of trace elements in complex aqueous – solid solution systems

Thermodynamics alone is usually not sufficient to predict growth-rate dependencies of trace element partitioning into host mineral solid solutions. In this contribution, two uptake kinetic models were analyzed that are promising in terms of mechanistic understanding and potential for implementation in geochemical modelling codes. The growth Surface Entrapment Model (Watson, 2004) and the Surface Reaction Kinetic Model (DePaolo, 2011) were shown to be complementary, and under certain assumptions merged into a single analytical expression. This Unified Uptake Kinetics Model was implemented in GEMS3K and GEM-Selektor codes (http://gems.web.psi.ch), a Gibbs energy minimization package for geochemical modelling. This implementation extends the applicability of the unified uptake kinetics model to accounting for non-trivial factors influencing the trace element partitioning into solid solutions, such as the changes in aqueous solution composition and speciation, or the depletion effects in closed geochemical systems.

Simultaneous Assessment of Uptake and Metabolism in Rat Hepatocytes: A Comprehensive Mechanistic Model

Kinetic parameters describing hepatic uptake in hepatocytes are frequently estimated without appropriate incorporation of bidirectional passive diffusion, intracellular binding, and metabolism. A mechanistic two-compartment model was developed to describe all of the processes occurring during the in vitro uptake experiments performed in freshly isolated rat hepatocytes plated for 2 h. Uptake of rosuvastatin, pravastatin, pitavastatin, valsartan, bosentan, telmisartan, and repaglinide was investigated over a 0.1 to 300 μM concentration range at 37°C for 2 or 45-90 min; nonspecific binding was taken into account. All concentration-time points were analyzed simultaneously by using a mechanistic two-compartment model describing uptake kinetics [unbound affinity constant (K(m,u)), maximum uptake rate (V(max)), unbound active uptake clearance (CL(active,u))], passive diffusion [unbound passive diffusion clearance (P(diff,u))], and intracellular binding [intracellular unbound fraction (fu(cell))]. When required (telmisartan and repaglinide), the model was extended to account for the metabolism [unbound metabolic clearance (CL(met,u))]. The CL(active,u) ranged 8-fold, reflecting a 11-fold range in uptake K(m,u), with telmisartan and valsartan showing the highest affinity for uptake transporters (K(m,u) <10 μM). Both P(diff,u) and fu(cell) span over two orders of magnitude and reflected the lipophilicity of the drugs in the dataset. An extended incubation time allowed steady state to be reached between media and intracellular compartment concentrations and reduced the error in certain parameter estimates observed with shorter incubation times. Active transport accounted for >70% of total uptake for all drugs investigated and was 4- and 112-fold greater than CL(met,u) for telmisartan and repaglinide, respectively. Modeling of uptake kinetics in conjunction with metabolism improved the precision of the uptake parameter estimates for repaglinide and telmisartan. Recommendations are made for uptake experimental design and modeling strategies.

Experimental and theoretical comparison of intracellular import of polymeric nanoparticles and small molecules: toward models of uptake kinetics

Central to understanding how nanoscale objects interact with living matter is the need for reproducible and verifiable data that can be interpreted with confidence. Likely this will be the basis of durable advances in nanomedicine and nanomedical safety. To develop these fields, there is also considerable interest in advancing the first generation of theoretical models of nanoparticle (NP) uptake into cells, and NP biodistribution in general. Here we present an uptake study comparing the outcomes for free molecular dye and NPs labeled with the same dye. A simple flux-based approach is presented to model NP uptake. We find that the intracellular NP concentration grows linearly in time, and that the uptake is essentially irreversible, with the particles accumulating in lysosomes. A wide range of practical challenges, from labile dye release to NP aggregation and the need to account for cell division, are addressed to ensure that these studies yield meaningful kinetic information. From the Clinical EditorThe authors present an uptake study comparing the outcomes for free molecular dye and NPs labeled with the same dye. A wide range of practical challenges are addressed including labile dye release, NP aggregation and the need to account for cell division with the goal that these studies yield meaningful kinetic information.

Cd(II) biosorption using Lessonia kelps

Lessonia kelps (L. trabeculata and L. nigrescens) have been successfully used for the recovery of Cd(II) from near neutral solutions. The biomass was pre-treated with calcium chloride for stabilization of alginate-based compounds. SEM–EDAX analysis and FT-IR spectrometry analysis were used for identifying the modifications of the biomass. Sorption isotherms were performed at the optimum pH (i.e., pH 6) and the maximum sorption capacity reached up to 1 and 1.5mmolCdg−1 for L. nigrescens (L.n.) and L. trabeculata (L.t.), respectively. The Langmuir equation fits well experimental data. The temperature (in the range 20-40°C) had a more marked effect on affinity coefficient than on maximum sorption capacity. The influence of particle size, sorbent dosage, metal concentration and temperature was evaluated on uptake kinetics. The kinetic profiles that were modeled using the Crank equation (i.e., the resistance to intraparticle diffusion) were hardly affected by the temperature and the particle size contrary to the sorbent dosage and the metal concentration, which show greater impact. The pseudo-second order rate equation was also tested for the modeling of uptake kinetics.

Muscle Strength and Metabolism in Master Athletes

Knee extensor muscle strength and metabolism were examined in endurance trained young versus master athletes (10 elderly: 62.5+/-4.1 yr and 10 young: 26.2+/-2.4 yr). Before and immediately after a resistance strength training (RST), subjects performed a maximal isometric voluntary contraction (MVC) and a 10-min cycling test at a same relative intensity. During MVC, evoked contractions of the knee extensors muscles were performed to assess neuromuscular properties. Metabolism was assessed using oxygen uptake kinetics model. Before the RST session master athletes showed lower knee extensors MVC values than young subjects (257 vs. 354 N p<0.05) without any difference in oxygen kinetics (respectively for elderly and young: oxygen slow component (VO2(sc)): 231 vs. 214 ml . min(-1) and time constant (tau1): 27.8 vs. 25.1 s, p>0.05). After the RST session, a similar effect of fatigue was observed on muscular properties and oxygen kinetics whatever the group (respectively for elderly and young: MVC: -13.4 vs. -15.9%; VO2(sc): +11.8 vs.+25.2% and tau1: -15.4 vs. -13.9%). Our results suggest that the ability of master athletes to perform exercise at a given intensity is maintained despite a significant loss in strength with ageing.