Evaluation of Biomedical Hydrogel Parameters for Biomolecular Diffusion in Controlled Drug Delivery
thesisposted on 2012-12-09, 00:00 authored by Mohammad Rahman
Hydrogels made of non-toxic poly(ethylene glycol) diacrylate (PEGDA) provide a suitable platform for controlled drug delivery. The effect of the hydrogel’s structural elements on the diffusive nature of therapeutic agent release from PEGDA hydrogels was examined. The system utilized the diffusive nature of biomolecules, such as matrix metalloproteinases (MMPs), to obtain a desired release profile. Hydrogels’ intrinsic physical properties influence the diffusivity of molecules. Thus, manipulation of physical properties by altercations in the structural elements of the gels provided control over the release of therapeutic agents. The microstructure of the hydrogel dictates the gel’s physical properties. Therefore, manipulation of physical properties can be monitored by changes in microstructural properties, such as mesh size. These manipulations were partly accomplished by varying the PEGDA molecular weight. Additionally, methoxy poly(ethylene glycol) monoacrylate (mPEGMA) tethers were incorporated into the hydrogel. The tether length was varied by using different mPEGMA molecular weights. This adds another layer complexity to the gel that can be manipulated in order to tailor it to a specific molecular diffusion profile. To elucidate the changes in small molecule diffusion caused by variations in the different gel components, diffusion was studied using 7-amino-4-methylcoumarin (AMC). The diffusion of AMC through hydrogels was measured using fluorescence spectroscopy in conjunction with a Franz cell apparatus. Also, a bovine serum albumin (BSA) diffusion study was conducted to examine the effects on the diffusion of biomolecules. The BSA diffusion study was completed using the same method as the previous study. This combination of studies and mesh size analysis showed that the diffusion rate is directly proportional to the increase in monomer molecular weight and mesh size but is inversely proportional to tether length.