The Effect of Polystyrene Nanoparticles Doped with Cationic and Anionic Block Copolymers on Serum Protein Adsorption

Abstract

The use of nanoparticles as novel therapeutic devices has the potential to revolutionize previous medicinal efforts. Polystyrene (PS) nanoparticles doped with a blend of neutral (PS-b-PEG), cationic (PS-b-DMAEMA), and anionic block copolymers (PS-b-PAA) were made using Flash NanoPrecipitation (FNP). Changing the pH of the formulations caused deprotonation/protonation of the hydrophilic blocks of the block copolymers functional groups, which changed the size. Next, we investigated the size behavior of PEGylated nanoparticles made with different compositions of the block copolymer; increasing the polyelectrolyte (PE):PEG ratio was found to generally decrease the size of nanoparticles. Next, we formulated nanoparticles doped with PS-b-PAA and PS-b-DMAEMA and characterized their sizes and zeta potentials. These sizes ranged from 50-150 nm. Because of limitations in centrifugation technology, nanoparticle sizes had to be increased to 150-200 nm. Because PS:PE ratio was found to be directly proportional to nanoparticle size, the ratios were empirically determined for each composition of block copolymer. Comparing the size-adjusted nanoparticles’ zeta potentials to those from the 1:1 PS:PE formulations, increasing the size can either (1) modify the “brush” surface configuration to that of a “mushroom” (PAA), or (2) reduce the repulsive forces that destabilize the nanoparticle via decreasing the surface density, favorably changing the zeta potential (DMAEMA). During protein adsorption, it was found that higher percentages of DMAEMA bound more bovine serum albumin (BSA) protein, especially 60% and 100% DMAEMA. Because albumin is generally negative, low adsorptions were observed with PAA-doped nanoparticles. Looking at the ratios between the concentration of the protein relative to the concentration of the block copolymer, a proposed upward and downward “step” relation was observed between percent DMAEMA and protein adsorption, and percent PAA and protein adsorption, respectively. Taking all factors into account, including zeta potential and protein adsorption, 75% DMAEMA and 25% PAA are the best nanoparticle formulations for their respective block copolymers. For DMAEMA, percent block copolymer, magnitude of zeta potential, and size are determining factors for amount of protein adsorbed. For PAA, these factors are independent of protein adsorption.