Rheological blends for drug delivery. I. Characterization in vitro.
Rheological blends of hyaluronic acid (HA) and hydroxypropylmethyl cellulose (HPMC) are attractive as injectable drug delivery vehicles given their shear thinning viscoelastic rheological properties and excellent biocompatibility. In this study, the rheological and water binding properties of HA-HPMC blends are investigated to optimize both the injectability and the drug release kinetics of polymer blends. The time required to release 75% of a bupivacaine payload was correlated with the overall polymer concentration of the blend and the water binding properties of the constituent polymers. This correlation enables the tuning of drug release kinetics over a range of several hours according to the total concentration and ratio of the polymers used in the blend. The injectability is also promoted by polymer blending; HPMC suppresses the high yield stress of HA solutions, whereas HA induces flow instabilities in the needle, which facilitate blend injection via plug flow. Consequently, significantly higher polymer concentrations can be injected as blends compared with that achievable with either of the polymers alone, extending the potential of these polymers for drug delivery.
Hoare
Todd
T
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Zurakowski
David
D
Langer
Robert
R
Kohane
Daniel S
DS
D000779:Anesthetics, Local / Q000008:administration & dosage / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry*; D002045:Bupivacaine / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D004548:Elasticity; D006820:Hyaluronic Acid / Q000737:chemistry*; D065347:Hypromellose Derivatives; D007700:Kinetics; D008422:Materials Testing; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D012212:Rheology; D014783:Viscosity
D000779:Anesthetics, Local; D001672:Biocompatible Materials; D065347:Hypromellose Derivatives; D006820:Hyaluronic Acid; D008747:Methylcellulose; D002045:Bupivacaine