Injectable intrathecal delivery system for localized administration of EGF and FGF-2 to the injured rat spinal cord.
The administration of growth factors (GFs) for treatment of experimental spinal cord injury (SCI) has shown limited benefits. One reason may be the mode of delivery to the injury site. We have developed a minimally invasive and safe drug delivery system (DDS) consisting of a highly concentrated collagen solution that can be injected intrathecally at the site of injury providing localized delivery of GFs. Using the injectable DDS, epidermal growth factor (EGF) and basic fibroblast growth factor (FGF-2) were co-delivered in the subarachnoid space of Sprague-Dawley rats. The in vivo distribution of EGF and FGF-2 in both injured and uninjured animals was monitored by immunohistochemistry. Although significant differences in the distribution of EGF and FGF-2 in the spinal cord were evident, localized delivery of the GFs resulted in significantly less cavitation at the lesion epicenter and for at least 720 mum caudal to it compared to control animals without the DDS. There was also significantly more white matter sparing at the lesion epicenter in animals receiving the GFs compared to control animals. Moreover, at 14 days post-injection, delivery of the GFs resulted in significantly greater ependymal cell proliferation in the central canal immediately rostral and caudal to the lesion edge compared to controls. These results demonstrate that the injectable DDS provides a new paradigm for localized delivery of bioactive therapeutic agents to the injured spinal cord.
Jimenez Hamann
Maria C
MC
Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto ON, Canada M5S-3E5.
Tator
Charles H
CH
Shoichet
Molly S
MS
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D004805:Ependyma / Q000187:drug effects / Q000502:physiology; D004815:Epidermal Growth Factor / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D007278:Injections, Spinal / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods; D051379:Mice; D008845:Microinjections / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods; D041681:NIH 3T3 Cells; D009410:Nerve Degeneration / Q000139:chemically induced / Q000503:physiopathology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013346:Subarachnoid Space / Q000187:drug effects / Q000502:physiology / Q000601:surgery; D016896:Treatment Outcome
D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor