Synthesis and engineering of polymeric latex particles for medical applications

Latex particles with well-defined colloidal and surface characteristics have received increasing attention due to their useful applications in many areas, especially as solid phase supports in numerous biological applications such as immunoassay, DNA diagnostic, cell separation, and drug delivery carrier. Hemodialysis membrane using these particles would be another potential application for the advanced separation treatment for patients with end stage renal disease (ESRD). It is desirable to remove middle molecular weight proteins with minimal removal of other proteins such as albumin. Thus, it is necessary to understand the fundamental interactions between the particles and blood proteins to maximize the performance of these membranes. This improvement will have significant economic and health impact.; The objective of this study is to synthesize polymeric latex particles of specific functionality to achieve the desired selective separation of target proteins from the human blood. Semi-continuous seed emulsion polymerization was used to prepare monodisperse polystyrene seed particles ranging from 126+/-7.5 to 216+/-5.3 nm in size, which are then enlarged by about 800nm. Surfactant amount played a key role in controlling the latex particle size. Negatively charged latex particles with a different hydrophobicity were prepared by introduction of a sodium persulfate initiator and hydrophilic acrylic acid monomer. The prepared polymeric particles include bare polystyrene (PS) particles, less hydrophobic PS core and PMMA shell particles, and more hydrophilic PS core and PMMA-co-PAA shell latex particles with a 370nm mean diameter. SEM, light scattering, and zeta potential measurements were used to characterize particle size and surface properties. Adsorption isotherms of two proteins, bovine serum albumin (BSA) and beta2-microglobulin (beta2M), on latex particles were obtained as a function of pH and ionic strength using the bicinchoninic acid (BCA) assay method. The Langmuir-Freundlich adsorption model was used to determine the adsorption amount of protein at equilibrium. The thickness of adsorbed BSA layer on latex particles was obtained in order to investigate the adsorption orientation such as end-on or side-on mode. Adsorption kinetics experiments for both proteins and all latex particles were also performed. The adsorption kinetic constant determined from the Langmuir-Freundlich adsorption isotherm model was used to calculate Gibbs free energy of adsorption to compare the competitive adsorption of BSA and W. Hemolysis tests were performed to investigate the blood compatibility of synthesized latex particles. PS/PMMA 90PAA10 and PS/PMMA75PAA25 core shell latex particles had desirable material properties with, not only a large amount and high rate of selective beta2M adsorption over BSA but also high blood compatibility showing less than 3% hemolysis.