Injectable microgel-hydrogel composites for prolonged small-molecule drug delivery.
The design and application of soft nanocomposite injectable hydrogels containing entrapped microgels for small-molecule drug delivery is demonstrated. Copolymer microgels based on N-isopropylacrylamide and acrylic acid were synthesized that exhibited both ionic and hydrophobic affinity for binding to bupivacaine, a cationic local anesthetic used as a model drug. Microgels were subsequently immobilized within an in situ-gelling hydrogel network cross-linked via hydrazide-aldehyde chemistry to generate hydrogel-microgel soft nanocomposites. Drug release could be sustained for up to 60 days from these nanocomposite hydrogels, significantly longer than that achievable using the constituent hydrogel or microgels alone (<1 week). Drug release kinetics could be readily tuned by varying the affinity of the microgel and hydrogel phases for drug-polymer interactions and the network density of the hydrogel phase.
Department of Chemical Engineering, McMaster University, Hamilton, Ontario, Canada L8S 4L7.
Daryl
D
Sivakumaran
Danielle
D
Maitland
Todd
T
Hoare
D000178:Acrylamides / Q000737:chemistry / Q000494:pharmacology; D000779:Anesthetics, Local / Q000737:chemistry; D000818:Animals; D002045:Bupivacaine / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D016503:Drug Delivery Systems; D006834:Hydrazines / Q000737:chemistry / Q000494:pharmacology; D020100:Hydrogels; D007267:Injections; D007700:Kinetics; D051379:Mice; D049329:Nanostructures / Q000737:chemistry; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology
D000178:Acrylamides; D000779:Anesthetics, Local; D004337:Drug Carriers; D006834:Hydrazines; D020100:Hydrogels; D011108:Polymers; D002045:Bupivacaine