Transport and interaction of ionizable drugs and proteins in hydrophilic polymers
Abstract
Solute/polymer interactions affect solute (drug and protein) diffusion in and release from swollen hydrophilic polymers. The use of environmentally responsive, pH-sensitive polymer networks further complicates the solute transport behavior by inducing changes in the polymer properties. In hydrophilic polymers containing ionizable pendant groups, the molecular weight between crosslinks, the degree of swelling, and the degree of ionization are altered by local changes in pH and ionic strength. Previous transport models for diffusion and interaction between solutes and ionizable polymers assume that the polymer consists of straight, cylindrical pores and that the solutes are rigid spheres. Although these assumptions are valid for track-etched membranes and filtration systems, they are not valid for the random mesh structure within hydrogels. A new model was developed based on free volume theory and the binding energy for the solute/polymer interactions measured with attenuated total reflectance-Fourier Transform Infrared (FTIR) spectroscopy. The results of the model indicated that the hindrance to diffusion due to solute/polymer interactions increased as the solute size was reduced. Ionizable pH-sensitive hydrogels were synthesized by free-radical polymerization of acrylic acid and 2-hydroxyethyl methacrylate with ethylene glycol dimethacrylate as crosslinking agent. The degree of crosslinking and degree of hydrophilicity were controlled by varying the relative concentration of crosslinking agent and comonomer, respectively. The hydrogel properties were characterized by gas chromatography, scanning electron microscopy, differential scanning calorimetry, titration, equilibrium and dynamic swelling, dextran permeation and FTIR spectroscopy. The role of solute distribution within the hydrogels as it related to the transport behavior was investigated by a procedure developed for hydrated samples which utilized cryotoming and FTIR-microscopy. The solute loaded hydrogels were cryotomed into 4 $\mu$m thin sections. The concentration profile of each solute was measured by monitoring the infrared vibrational band indicative of the solute, which was then plotted in two dimensions. These studies indicated that the solutes were evenly distributed throughout the bulk and surface of the hydrogel samples. The solute/polymer interactions were investigated as a function of the polymer composition, swelling media pH and solute size. The binding energy of the interaction was measured by the shift in the carbonyl peak of the acrylic acid which was involved in hydrogen bonding. It was found that the diffusional hindrance caused by the solute/polymer interactions was most significant for the smallest sized solutes, which correlated well with diffusion coefficients determined from transport studies performed on Valia-Chen diffusion cells.
Degree
Ph.D.
Advisors
Peppas, Purdue University.
Subject Area
Chemical engineering|Polymers|Pharmaceuticals
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