PEGylation of interleukin-10 for the mitigation of enhanced pain states.
J Biomed Mater Res A
; 93(3): 1169-79, 2010 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-19768789
ABSTRACT
The anti-inflammatory cytokine interleukin-10 (IL-10) shows promise for the treatment of neuropathic pain, but for IL-10 to be clinically useful as a short-term therapeutic its duration needs to be improved. In this study, IL-10 was covalently modified with polyethylene glycol (PEG) with the goal of stabilizing and increasing protein levels in the CSF to improve the efficacy of IL-10 for treating neuropathic pain. Two different PEGylation methods were explored in vitro to identify suitable PEGylated IL-10 products for subsequent in vivo testing. PEGylation of IL-10 by acylation yielded a highly PEGylated product with a 35-fold in vitro biological activity reduction. PEGylation of IL-10 by reductive amination yielded products with a minimal number of PEG molecules attached and in vitro biological activity reductions of approximately 3-fold. In vivo collections of cerebrospinal fluid after intrathecal administration demonstrated that 20 kDa PEG attachment to IL-10 increased the concentration of IL-10 in the cerebrospinal fluid over time. Relative to unmodified IL-10, the 20 kDa PEG-IL-10 product exhibited an increased therapeutic duration and magnitude in an animal model of neuropathic pain. This suggests that PEGylation is a viable strategy for the short-term treatment or, in conjunction with other approaches, the long-term treatment of enhanced pain states.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Dolor
/
Polietilenglicoles
/
Interleucina-10
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Biomed Mater Res A
Asunto de la revista:
ENGENHARIA BIOMEDICA
Año:
2010
Tipo del documento:
Article