(230a) Living Polymerization/Reaction Control: Innovative Strategies for Enhancing Drug Delivery From Imprinted Thin Films

Molecular imprinting allows for greater control of drug transport from hydrogels by the creation macromolecular memory for the drug/template molecule. Using living polymerization to create imprinted polymer networks is a more recent technique to enhance the effect of molecular imprinting. Here we will demonstrate that living polymerization leads to significantly enhanced binding parameters and delayed transport properties for drug molecules in weakly crosslinked aqueous polymers. Poly(HEMA-DEAEM-PEG200DMA) polymer gels were used as the drug delivery system with diclofenac, a non-steroidal anti-inflammatory drug, as the template molecule. Multiple gel compositions were created using both living and conventional free radical polymerization by varying the drug concentration present during polymerization, concentration of crosslinking monomer and solvent content in the pre-polymerization mixture. Template binding affinity and capacity were calculated using the Langmuir isotherm while the analysis of the polymer network was carried out using digital scanning calorimetry and gel permeation chromatography.

We demonstrate that using living polymerization results in a 38% increase in binding affinity and a 67% increase in capacity over the conventionally created hydrogel. By controlling the conversion further increases in capacity or affinity can be achieved adding greater tailorability to the hydrogel properties. Lastly, the drug release profile was extended two fold over conventionally created imprinted hydrogels and four fold over the non imprinted hydrogels. The observed enhancement in binding and transport properties may be explained by an extension of the chemically controlled chain propagation mechanism by the living polymerization technique. Thus, the results confirm that improved structural homogeneity of template binding sites and a global energy minimum of the spatial arrangement of polymer chains lead to enhanced binding parameters and delayed template release. This work will lead to a new generation of tailorable drug delivery biomaterials which can be designed from the molecular scale to yield exquisite control over controlled release of therapeutic drug molecules.