title: The control of cargo release from physically crosslinked hydrogels by crosslink dynamics.
abstract: Controlled release of drugs and other cargo from hydrogels has been an important target for the development of next generation therapies. Despite the increasingly strong focus in this area of research, very little of the published literature has sought to develop a fundamental understanding of the role of molecular parameters in determining the mechanism and rate of cargo release. Herein, a series of physically crosslinked hydrogels have been prepared utilizing host-guest binding interactions of cucurbit[8]uril that are identical in strength (plateau modulus), concentration and structure, yet exhibit varying network dynamics on account of the use of different guests for supramolecular crosslinking. The diffusion of molecular cargo through the hydrogel matrix and the release characteristics from these hydrogels were investigated. It was determined that the release processes of the hydrogels could be directly correlated with the dynamics of the physical interactions responsible for crosslinking and corresponding time-dependent mesh size. These observations highlight that network dynamics play an indispensable role in determining the release mechanism of therapeutic cargo from a hydrogel, identifying that fine-tuning of the release characteristics can be gained through rational design of the molecular processes responsible for crosslinking in the carrier hydrogels.
authors.affiliation: Melville Laboratory for Polymer Synthesis, Department of Chemistry, Cambridge University, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Appel
authors.affiliation: Melville Laboratory for Polymer Synthesis, Department of Chemistry, Cambridge University, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Forster
authors.affiliation: Melville Laboratory for Polymer Synthesis, Department of Chemistry, Cambridge University, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Rowland
authors.affiliation: Melville Laboratory for Polymer Synthesis, Department of Chemistry, Cambridge University, Lensfield Road, Cambridge CB2 1EW, UK. Electronic address: oas23@cam.ac.uk.
authors.forename: Oren A
authors.initials: OA
authors.lastname: Scherman
mesh_terms: D001952:Bridged-Ring Compounds / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D020100:Hydrogels / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils
chemical_list: D001952:Bridged-Ring Compounds; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D020100:Hydrogels; D007093:Imidazoles; D011108:Polymers; C507198:cucurbit(8)uril; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils
keywords: Controlled drug release; Cross-linking; Drug delivery; Drug release; Hydrogel; Mechanical properties