title: Novel intrathecal delivery system for treatment of spinal cord injury.
abstract: A novel, localized method for potential delivery of therapeutic agents to the injured spinal cord was investigated. The strategy consists of a polymeric drug solution that gels after injection into the subarachnoid space (SAS). By dispersing therapeutic agents in the polymeric solution, a method is provided for localized delivery to the spinal cord. To determine whether intrathecal injection of this drug delivery system (DDS) would affect cerebrospinal fluid (CSF) flow, a spinal canal model was built using dimensional analysis. Blocking up to 52% of the modeled subarachnoid space of the spinal canal caused minimal pressure differences (9.22 +/- 1.45 Pa), suggesting that implantation of a DDS would not subject the spinal cord to increased pressure. The safety of the DDS was also assessed in vivo by injecting collagen into the SAS of Sprague Dawley rats. Controls received injections of artificial CSF (aCSF). Collagen or aCSF was injected at the T2-T3 spinal level of both uninjured rats and rats injured with a 20g compression clip. The injected collagen persisted in the SAS for at least 8 weeks post-implantation and did not elicit an inflammatory reaction in either uninjured or injured animals. Long-term functional behavior was evaluated with the Basso, Beattie, and Bresnahan (BBB) scale weekly for 8 weeks. Functional behavior was similar in the collagen and aCSF groups, also indicating that the DDS was safe. This minimally invasive DDS may provide an alternative, safe method to deliver therapeutic agents intrathecally.
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Jimenez Hamann
authors.forename: Eve C
authors.initials: EC
authors.lastname: Tsai
authors.forename: Charles H
authors.initials: CH
authors.lastname: Tator
authors.forename: Molly S
authors.initials: MS
authors.lastname: Shoichet
mesh_terms: D020341:Absorbable Implants / Q000009:adverse effects; D000818:Animals; D001522:Behavior, Animal; D003094:Collagen / Q000008:administration & dosage*; D005260:Female; D007150:Immunohistochemistry; D020007:Implants, Experimental / Q000009:adverse effects; D007278:Injections, Spinal; D008959:Models, Neurological; D051381:Rats; D012449:Safety; D013115:Spinal Canal; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000628:therapy*; D013346:Subarachnoid Space / Q000502:physiology
chemical_list: D003094:Collagen