(217as) A Microfluidic Method to Evaluate Degradable Hydrogels for Drug Delivery

Diffusion in and degradation of dextran hydrogels was characterized in a microfluidic device and by complementary techniques. Microfluidic devices were prepared by crosslinking a formulation of dextran methacrylate (dex-MA) and photo-initiator, with and without visible dye, using photolithography to define a central microchannel. Channel sizes within the devices range from 300-1000 μm to simulate vessels within the body. The microfluidic technique allows for both image and effluent analyses. To visualize the diffusive behavior within the dextran hydrogel, methylene blue and Texas red dyes were used in both elution and uptake experiments.

The properties of the dex-MA hydrogel were characterized by the extent of crosslinking, the swelling ratio, and the mesh size of the gel. The structure of the hydrogel was related to the UV exposure dosage and the initial water and dye content in the dex-MA solution. Three analysis techniques for measuring diffusion coefficients were used to quantify the diffusion of solute in the hydrogel, including optical microscopy, characterization of device effluent, and NMR analyses. The optical microscopy technique analyzes images of the dye diffusion captured by a stereomicroscope to generate dye concentration v. position profiles. The data was fit to a diffusion model to determine diffusion coefficients and the dye release profile.

In a typical elution experiment, aqueous solution is pumped through the microchannel and dye diffuses out of the hydrogel and into the aqueous phase. During elution, images are taken at regular time intervals and the effluent was collected. Analysis of the device effluent was performed using ultraviolet-visible (UV/Vis) spectroscopy and high performance liquid chromatography (HPLC) to determine the effluent dye concentration and thus a short-time diffusion coefficient. Nuclear magnetic resonance (NMR) was used to determine a free diffusion coefficient of molecules in hydrogel without the effect of a concentration gradient. Diffusion coefficients for methylene blue and Texas red dye in dex-MA hydrogel calculated using the three analysis methods all agree well. It was determined that utilizing a combination of the three techniques offers greater insight into molecular diffusion in hydrogels than employing each technique individually. The optical and effluent methods were determined to be very effective for visualizing the diffusion and screening solutes to confirm that the solute is not just able to move within the hydrogel, but actually elute as well. Separately, to study degradation, the neat hydrogel was contacted by a dye-laden fluid in which the dye cannot diffuse into the non-degraded matrix. Over time, as the hydrogel degrades and there is greater free volume within the matrix, the dye is able to diffuse into the hydrogel, imparting color. The intensity of the color can be directly related to the degree of degradation, and the infiltration of dye can be compared to the degradation products quantified by HPLC. Implications for using hydrogels for controlled drug delivery are presented.