Intrathecal drug delivery strategy is safe and efficacious for localized delivery to the spinal cord

Abstract

Neuroprotective and neuroregenerative strategies for spinal cord injury repair are limited in part by poor delivery techniques. A novel drug delivery system is being developed in our laboratory that can provide localized release of therapeutically relevant molecules from an injectable hydrogel. Design criteria were established for the hydrogel to be--injectable, fast-gelling, biocompatible, biodegradable and able to release biologically active therapeutics when injected into the intrathecal space that surrounds the spinal cord. This novel way of localized drug delivery to the spinal cord was tested first with a collagen gel and then with a new hydrogel blend of hyaluronan and methylcellulose (HAMC). The underlying principle that this novel methodology is both safe and able to provide localized delivery was proven with a fast gelling collagen solution. Using a recombinant human epidermal growth factor, rhEGF, dispersed in collagen, we demonstrated localized release to the injured spinal cord. We extended this technology to other fast-gelling systems and found that HAMC was injectable due to the shear thinning property of hyaluronan (HA), biocompatible and had some therapeutic benefit when injected into the intrathecal space using a compression injury model in rats.