title: Tuning drug release from smart microgel-hydrogel composites via cross-linking.
abstract: Soft nanocomposite hydrogels consisting of thermoresponsive microgels physically entrapped or covalently cross-linked to a non-thermoresponsive hydrogel are synthesized and tested for their capacity to facilitate long-term drug release of a small molecule drug. Copolymer microgels based on N-isopropylacrylamide and acrylic acid were synthesized that exhibited ionic affinity for binding to bupivacaine, a cationic local anesthetic. These microgels were subsequently physically entrapped within an in situ-gelling carbohydrate-based hydrogel network cross-linked via hydrazide-aldehyde chemistry; alternately, hydrazide-functionalized microgels were prepared that covalently cross-linked to the bulk hydrogel phase. Both the overall rate of drug release and the magnitude of the burst release were significantly decreased when microgels were restricted from undergoing a phase transition between the preparation temperature of the nanocomposite (25°C) and the test temperature (37°C), whether deswelling was inhibited by increasing the cross-link density within the microgel itself or by cross-linking the microgel to the bulk hydrogel network. This result facilitates facile tuning of soft nanocomposite drug delivery systems to achieve targeted drug release kinetics.
authors.affiliation: Department of Chemical Engineering, McMaster University, 1280 Main St. W, Hamilton, Ontario, Canada L8S 4L7.
authors.forename: Daryl
authors.initials: D
authors.lastname: Sivakumaran
authors.affiliation: Department of Chemical Engineering, McMaster University, 1280 Main St. W, Hamilton, Ontario, Canada L8S 4L7.
authors.forename: Danielle
authors.initials: D
authors.lastname: Maitland
authors.affiliation: Department of Chemical Engineering, McMaster University, 1280 Main St. W, Hamilton, Ontario, Canada L8S 4L7.
authors.forename: Thomas
authors.initials: T
authors.lastname: Oszustowicz
authors.affiliation: Department of Chemical Engineering, McMaster University, 1280 Main St. W, Hamilton, Ontario, Canada L8S 4L7. Electronic address: hoaretr@mcmaster.ca.
authors.forename: Todd
authors.initials: T
authors.lastname: Hoare
mesh_terms: D000178:Acrylamides / Q000138:chemical synthesis / Q000737:chemistry; D000179:Acrylates / Q000138:chemical synthesis / Q000737:chemistry; D000777:Anesthetics / Q000737:chemistry*; D002045:Bupivacaine / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry*; D016503:Drug Delivery Systems; D005782:Gels / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure
chemical_list: D000178:Acrylamides; D000179:Acrylates; D000777:Anesthetics; D003432:Cross-Linking Reagents; D005782:Gels; C067295:N-isopropylacrylamide; C036658:acrylic acid; D002045:Bupivacaine