title: Sustained release of active chemotherapeutics from injectable-solid β-hairpin peptide hydrogel.
abstract: MAX8 β-hairpin peptide hydrogel is a solid, preformed gel that can be syringe injected due to shear-thinning properties and can recover solid gel properties immediately after injection. This behavior makes the hydrogel an excellent candidate as a local drug delivery vehicle. In this study, vincristine, a hydrophobic and commonly used chemotherapeutic, is encapsulated within MAX8 hydrogel and shown to release constantly over the course of one month. Vincristine was observed to be cytotoxic in vitro at picomolar to nanomolar concentrations. The amounts of drug released from the hydrogels over the entire time-course were in this concentration range. After encapsulation, release of vincristine from the hydrogel was observed for four weeks. Further characterization showed the vincristine released during the 28 days remained biologically active, well beyond its half-life in bulk aqueous solution. This study shows that vincristine-loaded MAX8 hydrogels are excellent candidates as drug delivery vehicles, through sustained, low, local and effective release of vincristine to a specific target. Oscillatory rheology was employed to show that the shear-thinning and re-healing, injectable-solid properties that make MAX8 a desirable drug delivery vehicle are unaffected by vincristine encapsulation. Rheology measurements also were used to monitor hydrogel nanostructure before and after drug encapsulation.
authors.affiliation: Department of Materials Science & Engineering, University of Delaware, Newark, DE 19176, USA. pochan@udel.edu.
authors.forename: Jessie E P
authors.initials: JE
authors.lastname: Sun
authors.forename: Brandon
authors.initials: B
authors.lastname: Stewart
authors.forename: Alisa
authors.initials: A
authors.lastname: Litan
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Lee
authors.forename: Joel P
authors.initials: JP
authors.lastname: Schneider
authors.forename: Sigrid A
authors.initials: SA
authors.lastname: Langhans
authors.forename: Darrin J
authors.initials: DJ
authors.lastname: Pochan
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D006207:Half-Life; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007267:Injections; D010455:Peptides / Q000737:chemistry*; D012212:Rheology; D053838:Scattering, Small Angle; D014750:Vincristine / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D010455:Peptides; D014750:Vincristine