(718b) Effect of Mesh Size and Polymer Composition in the Release Kinetics of Therapeutics From Imprinted Polymer Networks

Controlled drug release from hydrogels has been extensively studied for the past four decades. Major work has involved structural control over drug release. However, the field has done very little to understand the organization of the chemical functionality and orientation of polymer chains when a molecule that does not get covalently incorporated into the network is included in the polymerization. Imprinted network formation can lead to better control over the release profile and further delay release of drug due to the affinity relating to the number and strength of interactions between the drug and polymer network. Our group has demonstrated that macromolecular memory has led to desirable release control from weakly crosslinked thin polymer films. In this work, we tested the limits of this control altering composition, but more importantly, mesh size or spacing between polymer chains.

Thin hydrogel films, with the main chain building monomer being hydroxyl groups, were engineered and synthesized via biomimetic imprinting techniques to create macromolecular memory sites, which enhanced the loading and controlled the release of the non-steroidal anti-inflammatory diclofenac sodium (DS).  Diethylaminoethyl methacrylate (DEAEM) and N,N,N,N-diallyl dimethylammonium chloride (DADMAC) were selected as functional monomers. The concentration and length of the crosslinking monomer were important factors in determining the strength and the flexibility of the resultant network as well as the stability of the binding cavity formed by the imprinting process. The fractional mass released of DS in DI water increased as the length of the crosslinker was increased. Polymer films of significantly larger mesh size showed a release rate ~ 2.5 times faster than those with much smaller mesh sizes (4.5 times less), close to the size of the therapeutic. We attribute this to the difference in the structure which could make the macromolecular memory sites less stable and debilitated the ionic interaction between the anionic template molecule and the cationic functional monomers. Moreover, the release profiles in artificial lacrimal solution showed much faster releases compared to those performed in DI water.  The presence of salts and ions in the artificial lacrimal solution altered interactions between the anionic template molecule and the cationic functional monomers. Additional results using silicone hydrogel lenses pointed toward the increase of hydrophobic interactions on the chain level which could stabilize the ionic interaction achieving similar release profiles in lacrimal solution as DI water.

This work showed how structural properties such as mesh size can alter the structural conformation of the macromolecular memory sites within the polymer network, hence, changing the release kinetics of the drug. Understanding the structure of the macromolecular sites within imprinted polymer networks, will lead to biomaterials with better drug delivery control.