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

  • Hari Prasad Joshi
  • Sung Bum Kim
  • Seungki Kim
  • Hemant Kumar
  • Min-Jae Jo
  • Hyemin Choi
  • Juri Kim
  • Jae Won Kyung
  • Seil Sohn
  • Kyoung-Tae Kim
  • Jin-Ki KimEmail author
  • In-Bo HanEmail author


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 10 mg/kg/day, ip) once daily for seven consecutive days significantly reduced the mechanical allodynia and mechanical hyperalgesia compared with CORM-2 (10 mg/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-α, 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.


Neuropathic pain Nanoparticles Allodynia Hyperalgesia Carbon monoxide releasing molecule Carbon monoxide 



This research was supported by the National Research Foundation (NRF) of Korea (NRF2017R1C1B1011397) and Korea Health Technology Research and Development Project, Ministry for Health and Welfare Affairs (HI16C1559, HI18C0183). This work was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2017R1A2B4006458).

Author Contributions

IBH and JKK conceived and directed the project. IBH, HPJ, and HK designed the whole experimental plan. HPJ, MJJ, HC, JK, SK, and KW carried out the experiments. SBK, SS, and KTK analyzed the data and interpreted the result. IBH, HPJ, SBK, and SK wrote the paper. All authors reviewed the manuscript.

Compliance with Ethical Standards

Competing Interests

The authors declare that they have no competing interests.

Supplementary material

12035_2019_1468_MOESM1_ESM.docx (64 kb)
ESM 1 (DOCX 64 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019
corrected publication 2019

Authors and Affiliations

  1. 1.Department of Neurosurgery, CHA Bundang Medical Center, School of MedicineCHA UniversitySeongnam-siRepublic of Korea
  2. 2.Department of NeurosurgeryKyung Hee UniversitySeoulRepublic of Korea
  3. 3.Department of Surgery, CHA Bundang Medical Center, School of MedicineCHA UniversitySeongnam-siRepublic of Korea
  4. 4.Department of Neurosurgery, School of MedicineKyungpook National UniversityDaeguSouth Korea
  5. 5.Department of NeurosurgeryKyungpook National University HospitalDaeguSouth Korea
  6. 6.College of Pharmacy and Institute of Pharmaceutical Science and TechnologyHanyang UniversityAnsanRepublic of Korea

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