• Ryan Gene Soderquist, Evan M Sloane, Lisa C Loram, Jacqueline A Harrison, Ellen C Dengler, Scott M Johnson, Luke D Amer, Courtney S Young, Makenzie T Lewis, Stephen Poole, Matthew G Frank, Linda R Watkins, Erin D Milligan, and Melissa J Mahoney.
• Department of Chemical & Biological Engineering, University of Colorado at Boulder, 424 UCB, Boulder, Colorado, 80309, USA.
• Pharm. Res. 2010 May 1; 27 (5): 841-54.

PurposeInterleukin-10 (IL-10) is an anti-inflammatory molecule that has achieved interest as a therapeutic for neuropathic pain. In this work, the potential of plasmid DNA-encoding IL-10 (pDNA-IL-10) slowly released from biodegradable microparticles to provide long-term pain relief in an animal model of neuropathic pain was investigated.MethodsPLGA microparticles encapsulating pDNA-IL-10 were developed and assessed both in vitro and in vivo.ResultsIn vitro, pDNA containing microparticles activated macrophages, enhanced the production of nitric oxide, and increased the production of IL-10 protein relative to levels achieved with unencapsulated pDNA-IL-10. In vivo, intrathecally administered microparticles embedded in meningeal tissue, induced phagocytic cell recruitment to the cerebrospinal fluid, and relieved neuropathic pain for greater than 74 days following a single intrathecal administration, a feat not achieved with unencapsulated pDNA. Therapeutic effects of microparticle-delivered pDNA-IL-10 were blocked in the presence of IL-10-neutralizing antibody, and elevated levels of plasmid-derived IL-10 were detected in tissues for a prolonged time period post-injection (>28 days), demonstrating that therapeutic effects are dependent on IL-10 protein production.ConclusionsThese studies demonstrate that microparticle encapsulation significantly enhances the potency of intrathecally administered pDNA, which may be extended to treat other disorders that require intrathecal gene therapy.

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