title: An injectable drug delivery platform for sustained combination therapy.
abstract: We report the development of a series of physical hydrogel blends composed of hyaluronan (HA) and methyl cellulose (MC) designed for independent delivery of one or more drugs, from 1 to 28 days, for ultimate application in spinal cord injury repair strategies. To achieve a diversity of release profiles we exploit the combination of fast diffusion-controlled release of dissolved solutes from the HAMC itself and slow drug release from poly(lactide-co-glycolide) particles dispersed within the gel. Delivery from the composite hydrogels was demonstrated using the neuroprotective molecules NBQX and FGF-2, which were released for 1 and 4 days, respectively; the neuroregenerative molecules dbcAMP and EGF, and proteins alpha-chymotrypsin and IgG, which were released for 28 days. alpha-chymotrypsin and IgG were selected as model proteins for the clinically relevant neurotrophin-3 and anti-NogoA. Particle loaded hydrogels were significantly more stable than HAMC alone and drug release was longer and more linear than from particles alone. The composite hydrogels are minimally swelling and injectable through a 30 gauge/200 microm inner diameter needle at particle loads up to 15 wt.% and particle diameters up to 15 microm.
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, Canada. douglas.baumann@utoronto.ca
authors.forename: M Douglas
authors.initials: MD
authors.lastname: Baumann
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Kang
authors.forename: Jason C
authors.initials: JC
authors.lastname: Stanwick
authors.forename: Yuanfei
authors.initials: Y
authors.lastname: Wang
authors.forename: Howard
authors.initials: H
authors.lastname: Kim
authors.forename: Yakov
authors.initials: Y
authors.lastname: Lapitsky
authors.forename: Molly S
authors.initials: MS
authors.lastname: Shoichet
mesh_terms: D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D007267:Injections; D008747:Methylcellulose / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D013119:Spinal Cord Injuries / Q000188:drug therapy*
chemical_list: D020100:Hydrogels; D004364:Pharmaceutical Preparations; D006820:Hyaluronic Acid; D008747:Methylcellulose