Publication details

Authors: Nelson, D. M.; Ma, Z.; Leeson, C. E.; Wagner, W. R. 
Title: Extended and sequential delivery of protein from injectable thermoresponsive hydrogels 
Type: Journal Article 
Publisher: J Biomed Mater Res A 
Year: 2012 
Volume: 100 
Start Page: 776 
End Page: 785 
DOI: 10.1002/jbm.a.34015 
Abstract: Thermoresponsive hydrogels are attractive for their injectability and retention in tissue sites where they may serve as a mechanical support and as a scaffold to guide tissue remodeling. Our objective in this report was to develop a thermoresponsive, biodegradable hydrogel system that would be capable of protein release from two distinct reservoirs--one where protein was attached to the hydrogel backbone, and one where protein was loaded into biodegradable microparticles mixed into the network. Thermoresponsive hydrogels consisting of N-isopropylacrylamide (NIPAAm), 2-hydroxyethyl methacrylate (HEMA), and biodegradable methacrylate polylactide were synthesized along with modified copolymers incorporating 1 mol % protein-reactive methacryloxy N-hydroxysuccinimide (MANHS), hydrophilic acrylic acid (AAc), or both. In vitro bovine serum albumin (BSA) release was studied from hydrogels, poly(lactide-co-glycolide) microparticles, or microparticles mixed into the hydrogels. The synthesized copolymers were able to gel below 37 degrees C and release protein in excess of 3 months. The presence of MANHS and AAc in the copolymers was associated with higher loaded protein retention during thermal transition (45% vs. 22%) and faster release (2 months), respectively. Microspheres entrapped in the hydrogel released protein in a delayed fashion relative to microspheres in saline. The combination of a protein-reactive hydrogel mixed with protein-loaded microspheres demonstrated a sequential release of specific BSA populations. Overall the described drug delivery system combines the advantages of injectability, degradability, extended release, and sequential release, which may be useful in tissue engineering applications. 
Keywords: Acrylamides/chemistry, Acrylates/chemistry, Animals, Biocompatible Materials/chemistry/metabolism, Cattle, Drug Carriers/*chemistry/metabolism, Drug Delivery Systems/*methods, Hydrogels/*chemistry/metabolism, Injections, Materials Testing, Methacrylates/chemistry, Microspheres, Molecular Structure, Polyesters/chemistry, Polymers/chemistry, Serum Albumin, Bovine/chemistry/*metabolism, Temperature