A novel strategy for localized delivery of therapeutic agents to the injured spinal cord.

摘要

A novel method for localized delivery of therapeutic agents to the injured spinal cord was investigated. The strategy consists of a collagen solution that gels after injection into the subarachnoid space (SAS). By dispersing growth factors (GFs) in the collagen solution, a method is provided for localized delivery to the spinal cord. The initial goal was to determine the safety of implantation of the novel drug delivery system (DDS) in vivo by injecting collagen into the SAS of uninjured and spinal cord injured (SCI) rats. At 8 weeks post-implantation, the injected collagen did not elicit an inflammatory reaction in either uninjured or injured animals and did not affect the animals' functional behavior.; After verification of the safety of the DDS, the therapeutic value and efficiency of localized delivery of epidermal growth factor (EGF) and basic fibroblast growth factor (FG-2) were investigated. The DDS was injected intrathecaily at the site of injury in rats after compressive SCI. Animals receiving the GFs had a greater percentage of tissue spared at the lesion epicenter compared to controls which did not receive any injections. Moreover, there was greater ependymal cell proliferation immediately rostral and caudal to the injury. The efficiency of localized delivery of the GFs was evaluated by following their temporal and spatial distribution in vivo in both uninjured and SCI rodents for 30 minutes to 7 days after implantation of the DDS. EGF readily penetrated the spinal cord within 30 minutes post-injection. There was greater dispersion and more sustained penetration of EGF in SCI animals compared to uninjured rats at 6 hours post-injection. In contrast, the release of FGF-2 was slower and could only be detected in the pia and dura at the injection site at all time points examined. Improved functional recovery of SCI rats was not observed in animals receiving the DDS with GFs compared to control animals. However, the localized delivery of EGF and FGF-2 improved some outcome measures, such as decreased cavitation and increased ependymal cell proliferation. Thus, this novel DDS is a promising alternative method for localized delivery of therapeutic agents to the injured spinal cord.