Chinese Journal of Tissue Engineering Research ›› 2019, Vol. 23 ›› Issue (34): 5425-5429.doi: 10.3969/j.issn.2095-4344.1952

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Magnetic verapamil nanoparticles promote peripheral nerve regeneration

Zong Qiang1, Xu Yanan2, Qu Tianyi2, Li Lijun3, Hai Miti·Abuduaini3, Ni Dongkui3
  

  1. 1Department of Traumatology, 2Department of Emergency, Affiliated Yantai Hospital of Binzhou Medical University, Yantai 264100, Shandong Province, China; 3Department of Orthopedics, Second Hospital of Tianjin Medical University, Tianjin 300211, China
  • Received:2019-05-20 Online:2019-12-08 Published:2019-12-08
  • About author:Zong Qiang, Master, Physician, Department of Traumatology, Affiliated Yantai Hospital of Binzhou Medical University, Yantai 264100, Shandong Province, China
  • Supported by:

    the Scientific Research Foundation of Affiliated Yantai Hospital of Binzhou Medical University, No. BY2016KJ37 (to ZQ); Tianjin Health and Family Planning Commission Foundation, No. 2015KZ094 (to LLJ)

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Abstract:

BACKGROUND: Verapamil has been shown to effectively inhibit fibrosis and reduce scar. But its application is relatively limited in the repair of nerve scar.
OBJECTIVE: To investigate the effect of magnetic verapamil nanoparticles in the repair of sciatic nerve injury in rats.
METHODS: Verapamil was used as the model drug and poly(lactic-co-glycolic acid) as drug carrier to prepare verapamil nanoparticles and its physicochemical properties were characterized. Forty-five Sprague-Dawley rats (bought from Tianjin Aochen Laboratory Animals Co., Ltd., China) of specific-pathogen-free grade were chosen to establish rat models of the right sciatic nerve injury. Then these models were randomly divided into three groups: rats in the groups A and B were injected with magnetic verapamil nanoparticles via the tail vein once a week and their right lower limbs were exposed to the magnetic field for 2 hours. Rats in the group B received injection of magnetic verapamil nanoparticles via the tail vein once a week without exposure to the outside magnetic field. Rats in the group C received tail vein injection of verapamil solution once a week. The amount of verapamil injected was the same in the three groups. After 8 weeks of drug injection, electrophysiological examination of the proximal and distal sciatic nerve trunks was performed to measure the compound muscle action potential, and hematoxylin-eosin staining was also performed to observe right sciatic nerve regeneration and scar formation. This study was approved by the Medical Ethics Committee of Affiliated Yantai Hospital of Binzhou Medical University (approval No. F-KY-0022-20161201-01).
RESULTS AND CONCLUSION: Magnetic verapamil nanoparticles were spherical with the mean diameter of 208.3±0.8 nm, encapsulation efficiency of (70.21±3.25)%, and drug loading rate of 5.23%, respectively. They exhibited good release effect in vitro. MRI showed that the mean T2 value of the right lower limbs of rat models of sciatic nerve injury was 327.48, and it was 235.71 in the group B and 168.79 in the group A. The nerve conduction velocity in the group A was significantly greater than that in the groups B and C (P < 0.05), and there was no significant difference in nerve conduction velocity between groups B and C (P > 0.05). Hematoxylin-eosin staining revealed that in the group A, the nerve fibers in the anastomosis site were arranged neatly and there were few scars. In the groups B and C, the nerve fibers in the anastomosis site were poorly arranged and there were many scars. These results suggest that magnetic verapamil nanoparticles can promote the recovery of rat sciatic nerve injury.

Key words: magnetic verapamil nanoparticles, verapamil, poly(lactic-co-glycolic acid), nanoparticle, outside magnetic field, magnetic targeting, magnetic resonance imaging, sciatic nerve injury, nerve repair

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