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Nanocarrier-mediated Delivery of CORM-2 Enhances Anti-allodynic and Anti-hyperalgesic Effects of CORM-2

Title
Nanocarrier-mediated Delivery of CORM-2 Enhances Anti-allodynic and Anti-hyperalgesic Effects of CORM-2
Author
김진기
Keywords
Neuropathic pain; Nanoparticles; Allodynia; Hyperalgesia; Carbon monoxide releasing molecule; Carbon monoxide
Issue Date
2019-08
Publisher
SPRINGER
Citation
MOLECULAR NEUROBIOLOGY, v. 56, No. 8, Page. 5539-5554
Abstract
Neuropathic pain is a devastating chronic condition and effective treatments are still lacking. Carbon monoxide-releasing molecule-2 (CORM-2) as a carbon monoxide (CO) carrier, exerts potent anti-neuropathic pain effects; however, its poor water solubility and short half-life hinder its clinical utility. Therefore, the aim of this study was to investigate whether CORM-2-loaded solid lipid nanoparticles (CORM-2-SLNs) enhance the anti-allodynic and anti-hyperalgesic effects of CORM-2 in a rat chronic constriction injury (CCI) model. CORM-2-SLNs were prepared using a nanotemplate engineering technique with slight modifications. The physiochemical properties of CORM-2-SLNs were characterized and CO release from CORM-2-SLNs was assessed using a myoglobin assay. CO was slowly released from CORM-2-SLNs, was observed, and the half-life of CO release was 50 times longer than that of CORM-2. In vivo results demonstrate that intraperitoneal administration of CORM-2-SLNs (5 and 10mg/kg/day, ip) once daily for seven consecutive days significantly reduced the mechanical allodynia and mechanical hyperalgesia compared with CORM-2 (10mg/kg/day, ip). RT-PCR and Western blot analyses on days 7 and 14, revealed that treatment with CORM-2-SLNs resulted in greater reductions in the CCI-elevated levels of heme-oxygenase-2 (HO-2); inducible nitric oxide synthase (iNOS); neuronal NOS (nNOS); and inflammatory mediators (TNF-alpha, IBA-1, and GFAP) in the spinal cord and dorsal root ganglions compared with treatment with CORM-2. In contrast, HO-1 and IL-10 were significantly increased in the CORM-2-SLN-treated group compared with the group treated with CORM-2. These data indicate that CORM-2-SLNs are superior to CORM-2-S in alleviating mechanical allodynia and mechanical hyperalgesia.
URI
https://link.springer.com/article/10.1007%2Fs12035-019-1468-7https://repository.hanyang.ac.kr/handle/20.500.11754/121325
ISSN
0893-7648; 1559-1182
DOI
10.1007/s12035-019-1468-7
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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