Rational evaluation of the utilization of PEG-PEI copolymers for the facilitation of silica nanoparticulate systems in biomedical applications.

HYPOTHESIS: Polymer constructs are often applied in nanoparticulate systems to expand their applicability. One such common macromolecular modifier is poly(ethylene imine) - poly(ethylene glycol) copolymers. Despite their quite widespread use, and considering that interaction and stabilization mechanisms when combining a polyelectrolyte with a non-charged polymer are not trivial to pinpoint, these systems are generally poorly characterized in literature. Here, we attempt to provide a solid rationale to utilize PEG-PEI copolymers as surface modifiers and stabilizers/dispersion agents in solid colloidal systems with focus on biomedical applicability. EXPERIMENTAL: mPEG grafted PEI copolymers with two different grafting densities and 100 nm sized non-porous silica nanoparticles (SiNP) were synthesized. Detailed physico-chemical characterization of all prepared materials was conducted with spectroscopic methods, while the interaction mechanisms between the produced copolymers and SiNP were investigated by calorimetry. The influence of increased PEG grafting ratio on the attained colloidal stability of copolymer functionalized SiNP was studied by multiple light scattering, and its further implications on the biobehavior of SiNP were evaluated. FINDINGS: The interaction mechanism between SiNP and copolymers was concluded to be mainly directed by electrostatics, whereas an influence of PEG grafting density on the adsorption process was also observed. The implications of the surface modifications on the in vitro biobehavior of SiNP were investigated by combining the knowledge obtained by the detailed characterizations with microscopy evaluation under in vitro conditions.

Influence of Diffusion on the Kinetics of an Enzyme-Catalyzed Reaction in Gelatin-Based Gels.

The influence of mass-transport limitations on the initial reaction rates of a lipase-catalyzed stereoselective esterification reaction has been investigated for two structurally different gelatin-based gels. The time to reach equilibrium is much longer in pelleted hydrogels (pseudo-solid aqueous gels; PAGs) than in pelleted microemulsion-based gels (MBGs). R/S-(+/-)-2-Octanol and hexanoic acid were used as substrates. The reaction takes place by imbibition of the substrate-containing organic solvent into pores of the pelleted gel. To minimize the diffusion distances, the macroscopic surface areas of the gels were increased by granulating the gel pellets. The experimentally obtained initial reaction rates in granules were in good agreement with the theoretically obtained values from extrapolation to infinitely large areas. However, the still low initial reaction rates in the hydrogels compared to those in microemulsion-based gels cannot be explained by diffusion limitations. This finding was supported by the similar activation energies in both gels in granulated form. Changes in apparent molar standard enthalpy, entropy, and Gibbs energy for the activated complex formation were also estimated. The low reaction rate in hydrogels might thus be due to partial denaturation of the enzyme during the preparation step, to higher surface energy, or to the influence of a different solvent environment on the enzyme in these gels than in the microemulsion-based gels. Copyright 2001 Academic Press.