Modeling of immunoglobulin uptake by N,N,N′,N′-ethylenediaminetetramethylenephosphonic acid-modified zirconia particles under static and dynamic conditions

Abstract

A matrix developed from N,N,N',N'-ethylenediaminetetramethylenephosphonic acid-modified zirconia beads (further referred to as r_PEZ); 25-38 microm in diameter and with a pore size of 22+/-3 nm, was utilized for the separation of immunoglobulins (Igs). r_PEZ has been shown to bind to various Igs originating from a wide variety of species. To understand the mechanisms controlling the uptake of Igs by r_PEZ, static protein uptake experiments were carried out. The protein uptake profiles were further modeled with a kinetic rate constant model. Individual studies were undertaken for human immunoglobulin A, G and M (HIgA, HIgG and HIgM). The kinetic rate constant model indicated that HIgG binding to r_PEZ was more favorable than its disassociation. The equilibrium rate constants were found to decrease with increasing concentration. The effect of continuous loading in a packed bed system utilizing r_PEZ matrix was evaluated by carrying out frontal studies, using different feed concentrations and linear velocities. The breakthrough profiles obtained for the uptake of HIgG were modeled with the pore diffusion model. The model was found to best describe the breakthrough profiles obtained at a feed concentration of 2.0 mg of HIgG per milliliter. The NTU for the packed bed was found to be equal to 2.

Impact of Porogens on the Pore Characteristics of Zirconia Particles Made by Polymer-Induced Colloid Aggregation

“…6,31,32 An examination of the relationship between the size of the colloid and the pore size obtained in aggregates obtained by the spray drying process, the PICA process, or the oilemulsion process reveals that when a colloidal solution (with the colloid particle size of 100 nm (1000 Å)) was used in any of the aggregation processes listed, a pore size in the range of 1827 nm was often obtained. 3,[33][34][35] In the absence of porogen or any binder molecule, we hypothesize that the most viable arrangement of col loid particles is one in which three colloid particles are held in the cluster. The resultant pore diameter ob tained equals the equivalent diameter of the interstitial void space between colloid particles.…”