Release of plasmid DNA-encoding IL-10 from PLGA microparticles facilitates long-term reversal of neuropathic pain following a single intrathecal administration.
Pharm Res
; 27(5): 841-54, 2010 May.
Article
en En
| MEDLINE
| ID: mdl-20224990
ABSTRACT
PURPOSE:
Interleukin-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.METHODS:
PLGA microparticles encapsulating pDNA-IL-10 were developed and assessed both in vitro and in vivo.RESULTS:
In 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.CONCLUSIONS:
These 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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Plásmidos
/
ADN
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Terapia Genética
/
Interleucina-10
/
Técnicas de Transferencia de Gen
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Enfermedades del Sistema Nervioso Periférico
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Pharm Res
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos