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Release of biomolecules from hydrogel matrices of photopolymerized poly(ethylene glycol)

Posted on:2002-02-23Degree:Ph.DType:Dissertation
University:Texas A&M UniversityCandidate:Mellott, Michael BFull Text:PDF
GTID:1461390011990728Subject:Engineering
Abstract/Summary:
Sustained drug delivery from hydrogel matrices can be used to replace the daily oral administration of drugs. By encapsulating drugs in a highly crosslinked poly(ethylene glycol) diacrylate (PEG-DA) hydrogel sphere, a sustained release of drugs while retaining activity can be achieved.; Highly crosslinked hydrogel spheres were fabricated using UV photopolymerization of PEG-DA. A photoinitiator, which cleaves into reactive free radicals upon exposure to UV light, was used to polymerize the hydrogels. A crosslinking agent (pentaerythritol triacrylate, PETA) and a comonomer (acrylic acid, acrylamide, allylamine, or allyl alcohol) were added to change the chemical properties of the hydrogels to affect release characteristics. Photopolymerization rates and polymer morphology were determined using attenuated total reflectance/Fourier transform infrared spectroscopy and electron microscopy, respectively.; Hydrogels were extensively characterized for physical properties including volume change upon hydration (56.8%, all values for hydrogels with no comonomer, no crosslinker), equilibrium water content (49.4), diffusivity of the expanding gel network (5.08 × 10−6 cm2/second), molecular weight between crosslinks (72.3 g/mol), and polymer mesh size (23.0 Å). The effect of PETA and comonomer concentration upon these properties was determined.; Release from polymer matrices can have many advantages including local delivery, sustained and controlled release, and protection of the drug from the environment. Bovine serum albumin was incorporated into the hydrogel to simulate delivery of a model protein drug. The effective diffusion coefficients, based on a Fickian release model, were calculated to be 4.29 × 10 −10 cm2/second. Horseradish peroxidase was then incorporated and released upon hydration. Approximately 65% of the protein released on the first day of release was deactivated by a combination of polymerization and storage in the hydrogel.; PEG-DA array elements (500 μm diameter, 12 μm height) were microfabricated onto a planar silicon surface to be used as an array of release elements. The array could then be coupled with a device to be used in vivo. The array would allow for local delivery of a drug and would not fail if a small number of elements malfunctioned. When basic fibroblast growth factor (bFGF) was incorporated into the elements, release of active bFGF was detected for over 4 days.
Keywords/Search Tags:Release, Hydrogel, Matrices, Polymer, Used, Drug, Elements, Delivery
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