Traumatic spinal cord injury (SCI) causes partial or complete loss of sensory, motor, and autonomic functions below the injury site. Patients with SCI suffer lifelong disability and require continuous physical and medical care. It is a leading cause of permanent disability in young adults. The initial trauma is followed by a wave of secondary injury cascades that leads to a cavity many times bigger than the initial lesion and often causes deleterious functional loss. Many mechanisms contribute to the secondary injury cascades following traumatic spinal cord injury (SCI). However, most current treatment strategies only target one or a few elements in the injury cascades, and have been largely unsuccessful in clinical trials. Minocycline hydrochloride (MH) is a highly promising therapeutic intervention for SCI because it has been shown to target a broad range of secondary injury mechanisms via its anti-inflammatory, anti-oxidant, and anti-apoptotic properties. However, MH is only neuroprotective at high concentrations. The inability to translate the high doses of MH used in experimental animals to tolerable doses in human patients limits its clinical efficacy. In addition, the duration of MH treatment is limited because long-term systemic administration of high doses of MH has been shown to cause liver toxicity and even death.

In this study, we have developed a drug delivery system in the form of hydrogel loaded with polysaccharide-MH complexes self-assembled by metal ions for controlled MH release. This drug delivery system can be implanted or injected into the intrathecal space for non-invasive local delivery of MH with sufficient dose and duration. We investigated the factors that control MH release, and developed fomulations with release profiles that are relavent to the progression of secondary injury processes. We show that in a clincially relevant unilateral cervial spinal cord contusion injury model, both immediate and delayed local MH treatments were effective in reducing secondary injury and promoting locomotor functional recovery. In addition, we studied MH biodistribution in local spinal cord tissue, CSF, and serum.