Simulated blood plasma

Covington AK, Ferra MIA. Calculation of single ion activities in solutions simulating blood plasma. In Maas AHJ, ed. Methodology and clinical appHcations of ion selective electrodes. Copenhagen International Federation of Clinical Chemistry, 1986 239-47. 

Ishikawa K, Takagi S, Chow LC, Ishikawa Y, Eanes ED, Asaoka K. Behavior of a calcium phosphate cement in simulated blood plasma in vitro. Dent Mater. 1994 Jan 10(1) 26-32. 

After setting of the cement, gradual phase transformation of the Ca-P compounds occurs into more apatitic phases. Due to the nonsintered nature and the higher surface area of Ca-P cements, dissolution of calcium and phosphate ions in physiological conditions occurs to a higher extent than in sintered ceramics. However, the relatively large surface area in combination with supersaturated body fluids also results in high Ca-P precipitation. Ishikawa et al. [23] reported that the total precipitation of (B-type) carbonate HA at the surface of Ca-P cement increased the total surface dissolution in simulated blood plasma in vitro for a period of 20 weeks. In vivo, formation of carbonated HA on cement surface has been reported to occur within 12 h of implantation [24]. This phenomenon could be one of the essential aspects of the exceptionally positive osteoconductive behavior of Ca-P cements. 

Only a subset of the parameter values in the O Flaherfy model require inputs from the user to simulate blood and tissue lead concentrations. Lead-related parameters for which values can be entered into the model include fractional absorption from the gastrointestinal tract partition coefficients for lead in nonbone tissues and in the surface region of bone maximum capacity and half-saturation concentration for capacity-limited binding in the erythrocyte elimination clearance fractional clearance of lead from plasma into forming bone and the restricted permeability coefficients for lead diffusion within bone, from plasma into bone, and from bone into plasma (O Flaherty 1991a). 

Kokubo et al. [16,17] showed that the hydroxyapatite formation on the surfaces of bioactive materials in the living body can be reproduced even in an acellular protein-free simulated body fluid (SB F) with ion concentrations nearly equal to those of human blood plasma. This indicates that the hydroxyapatite layer is formed through chemical reaction of the bioactive glass with the surrounding body fluids. The formed layer consists of carbonated hydroxyapatite with small crystallites and low crystallinity, which is similar to bone hydroxyapatite. Hence the bioactivity of a material can be evaluated even in vitro by examining the hydroxyapatite formation on its surface in SBF. 

As with classic compartment pharmacokinetic models, PBPK models can be used to simulate drug plasma concentration versus time profiles. However, PBPK models differ from classic PK models in that they include separate compartments for tissues involved in absorption, distribution, metabolism and elimination connected by physiologically based descriptions of blood flow (Figure 10.1). 

Table 4 Percentage Occurrence of the Major Complexes (Non-protein) in Blood Plasma from Computer Simulation -1 ...

From potentiometric and spectroscopic studies it is concluded that the main species at neutral pH is a 1 1 tridentate chelate (11) with a log stability constant of ca. — 4. The claim55 that the stability of this species is comparable to that of the Cu(albumin) complex is rather surprising, since for this to occur the involvement of a histidine in the third amino add position is normally required, and furthermore others have concluded that in blood plasma at least the tripeptide is unlikely to compete against other ligands for the available Cu11.56,57 To illustrate the point that such conclusions from blood plasma simulations are only applicable to that medium, Pickart and Thaler58 have shown that in a cell culture medium the tripeptide considerably enhanced Cu uptake into cells and that this was not affected by a 300-fold molar excess of amino adds, including histidine. 

May P. M., Linder P. W., and Williams D. R. (1977) Computer simulation of metal-ion equilibria in biofluids models for the low-molecular-weight complex distribution of calciu-m(II), magnesium(II), manganese(II), iron(III), copper(II), zinc(II), and lead(II) ions in human blood plasma. J. Chem. Soc. Dalton Trans. 588—595. 

J.R. Dufheld, P.M. May, and D.R. Williams, Computer Simulation of Metal Ion Equilibria in Biofluids, No. 4, Plutonium Speciation in Blood Plasma and Chelation Therapy , J. Inorg. Biochem., 1984. 20, 199-214. 

Canham LT, Reeves CL, Newey LP, Houlton MR, Cox TI, Buriak J, Stewart MP (1999) Derivatized mesoporous silicon with dramatically improved stabdity in simulated human blood plasma. Adv Mater 11 1505-1507... 

For animal fluids, amino add and protein binding appear to dominate for the trace elements. However, for Ca " and Mg citrate binding may well occur. A computer simulation exercise on blood plasma (further details in Section 22.3) suggests approximately 5% of these metal ions are in the form of dtrate complexes. The same exerdse indicates that any Fe" present would be totally bound in anionic citrate species. Interestingly the greater zinc nutritional value of human milk as opposed to bovine milk is related to zinc being present as labile citrate complexes in the former but as a tightly bound protein complex in the latter. ... 

Solution formulations commonly used In the culturing of mammalian cells were the major inspiration points for the current study. Cell culture solutions, which were developed decades before the Kokubo SBF [30, 31], contain Ca, Mg Na+, K+, HP04 , Cl" and HCOs" ions in concentrations similar to those found In the blood plasma. A recent article by Boccaccini et al. [37] disclosed that the Trls-buffer present In the SBF (simulated/synthetic body fluid)... 

Posner clusters i.e., Cag(P04)6), with sizes close to 0.8 nm, are present in supersaturated and metastable CaP solutions claimed to simulate the electrolyte portion of blood plasma, as experimentally proved by Oyane etal. using dynamic light scattering [49]. Directly quoting from the work of Posner [50, 51], in the process of AGP formation in solution, Ca9(P04)6 clusters form first (with the experimental support to this provided by the later work of Oyane et al. [49]) and then are aggregated randomly to produce the larger spherical particles with the inter-duster space filled with water. The solution of Table 1 shall have the similar Posner dusters prior to its in sfru precipitation of AGP when it is warmed up. 

The bioactivity of the PCL-Si02 hybrid system demonstrated by the formation of a layer of hydroxyapatite on the surface of samples soaked in a fluid simulating the composition of human blood plasma [358, 361]. Studies on the bioactivity of PMMA-Si02 nanohybrid materials has indicated that they are suitable materials for use as bioactive bone substitutes or as nanofillers for PMMA bone cement [362]. 

TABLE 14.1.3 Ion concentrations of human blood plasma and simulated body fluid (SBF)... 

Derivatized mesoporous silicon with dramatically improved stability in simulated human blood plasma. Adv Mater 11 1505-1507... 

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