(162n) Complementary Techniques of Measuring Degradation and Diffusion in Hydrogels for Controlled Drug Delivery

Hydrogels are becoming of increasing interest in drug delivery research, specifically, injectable hydrogels that gel in physiological conditions without the formation of radical reactive species, and without the need for UV light exposure. Additionally, hydrogels that can degrade in a relevant amount of time, according to their specific purpose, are important, as they eliminate the need for recovery of the hydrogel, via surgery, after their purpose has been served.

Current degradation studies on hydrogel systems often study the hydrogel in excess amounts of aqueous solution in systems that do not closely resemble physiological conditions. The conditions that can be obtained using microfluidics, which utilizes microchannels with dimensions in the range of tens to hundreds of microns, are able to more accurately measure hydrogel swelling, degradation, and diffusion in a more biologically relevant environment. This research seeks to demonstrate the validity of using a microfluidic method to characterize the degradation and diffusion behavior of hydrogels.

The microfluidic devices consist of hydrogel cured around a central microfluidic channel, through which aqueous solution is flowed. The degradation and swelling behaviors of the hydrogels can be observed through changes in the width of the channel, as the hydrogel swells into the channel, and degrades and recedes away from the channel. Through the use of microscopes with image capturing capabilities, the change in microchannel dimension can be monitored and coupled with information found from chemical analysis of degradation products in the effluent fluid exiting the channel. In addition, diffusion of model drug molecules, into and out of the hydrogel, can be observed optically, in the case of dyes, as well as with analysis of the effluent fluid exiting the device.

Using Diffusion Ordered Spectroscopy (DOSY), more accurate values regarding diffusion can be found for the hydrogel systems, to be used for comparison. Since the hydrogel systems being studied cure thermally, it is possible that DOSY NMR measurements can be taken throughout the course of gelation, granted the gelation occurs over a long enough time to allow for sufficient measurements to be taken.

A previously described injectable hydrogel, formed via the thiol-ene Michael addition of ethoxylated trimethylolpropane tri-3-mercaptopropionate (ETTMP) and poly(ethylene glycol) diacrylate (PEGDA), thermally cures at 37°C, and is the initial hydrogel chosen as the model for these studies. This hydrogel exhibits thermoresponsive swelling behavior when in an aqueous environment, and the microfluidic measurements are being used to study the swelling behavior at various temperatures. This will be coupled with DOSY NMR measurements, at various temperatures, to measure how diffusion is changing with the change in temperature, to be able to characterize these thermoresponsive network changes. These complementary methods will be used to give a more complete picture of the behavior of the hydrogel, to better predict its behavior in the body.

The goal of this work is to extend these methods to studying other injectable, degradable hydrogel systems, including a hydrogel shown to degrade in acidic conditions that is formed via the amine-yne click reaction between carboxymethyl chitosan (CMC) and a 2-arm PEG monomer functionalized with an electron-deficient alkyne. To create more injectable hydrogel systems formed via click reactions, the thiol-yne click hydrogel formed via addition of ETTMP and the alkyne derivatized PEG monomer is being developed and has successfully been cured. In addition, a hydrogel formed via the click reaction between the amine and acrylate of CMC and PEGDA, respectively, is being developed, leading to the possibility of four PEG based, injectable hydrogel systems formed via click reactions from these four monomers, that can be tested using these complementary degradation and diffusion studies.