Accelerated release of a sparingly soluble drug from an injectable hyaluronan-methylcellulose hydrogel

An injectable hydrogel, comprised of hyaluronan and methylcellulose (HAMC), shows promise for localized, sustained delivery of growth factors for treatment of spinal cord injury (SCI). To better understand its potential for the delivery of small molecules, the release of sparingly soluble neuroprotectant, nimodipine, was investigated experimentally and via continuum modeling. This revealed that the MC in HAMC increased the solubility of sparingly soluble drug by over an order of magnitude, and enabled highly tunable release rates to be achieved by varying the method by which the drug was introduced into the scaffold. When nimodipine was introduced into HAMC in solubilized form, it was rapidly released from the scaffold within 8 h. Conversely, when nimodipine was blended into HAMC in particulate form, the release rates were greatly reduced, giving rise to complete release over 2-3 days for small, sub-micron particles, and longer times for large, 100 mum particles. The nimodipine particle-loaded gels yielded particle size-dependent, biphasic release profiles, which reflected rapid release of the solubilized drug followed by the slow, dissolution-limited release of solid nimodipine. This suggests that injectable hydrogel matrices can act as polymeric excipients that accelerate the delivery of poorly soluble drugs and yield highly tunable release rates.