Ultrasonographic Contrast and Therapeutic Effects of Hydrogen Peroxide-Responsive Nanoparticles in a Rat Model with Sciatic Neuritis

Int J Nanomedicine. 2024 Mar 27:19:3031-3044. doi: 10.2147/IJN.S447691. eCollection 2024.

Abstract

Purpose: Peripheral nerve damage lacks an appropriate diagnosis consistent with the patient's symptoms, despite expensive magnetic resonance imaging or electrodiagnostic assessments, which cause discomfort. Ultrasonography is valuable for diagnosing and treating nerve lesions; however, it is unsuitable for detecting small lesions. Poly(vanillin-oxalate) (PVO) nanoparticles are prepared from vanillin, a phytochemical with antioxidant and anti-inflammatory properties. Previously, PVO nanoparticles were cleaved by H2O2 to release vanillin, exert therapeutic efficacy, and generate CO2 to increase ultrasound contrast. However, the role of PVO nanoparticles in peripheral nerve lesion models is still unknown. Herein, we aimed to determine whether PVO nanoparticles can function as contrast and therapeutic agents for nerve lesions.

Methods: To induce sciatic neuritis, rats were administered a perineural injection of carrageenan using a nerve stimulator under ultrasonographic guidance, and PVO nanoparticles were injected perineurally to evaluate ultrasonographic contrast and therapeutic effects. Reverse transcription-quantitative PCR was performed to detect mRNA levels of pro-inflammatory cytokines, ie, tumor necrosis factor-α, interleukin-6, and cyclooxygenase-2.

Results: In the rat model of sciatic neuritis, PVO nanoparticles generated CO2 bubbles to increase ultrasonographic contrast, and a single perineural injection of PVO nanoparticles suppressed the expression of tumor necrosis factor-α, interleukin-6, and cyclooxygenase-2, reduced the expression of F4/80, and increased the expression of GAP43.

Conclusion: The results of the current study suggest that PVO nanoparticles could be developed as ultrasonographic contrast agents and therapeutic agents for nerve lesions.

Keywords: contrast media; hydrogen peroxide; neuroinflammation; polymer nanoparticles; ultrasonography.

MeSH terms

  • Animals
  • Benzaldehydes*
  • Carbon Dioxide
  • Cyclooxygenase 2 / metabolism
  • Humans
  • Hydrogen Peroxide / metabolism
  • Interleukin-6 / metabolism
  • Nanoparticles* / chemistry
  • Rats
  • Sciatic Nerve / diagnostic imaging
  • Sciatic Nerve / metabolism
  • Sciatic Neuropathy* / metabolism
  • Sciatic Neuropathy* / pathology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • vanillin
  • Hydrogen Peroxide
  • Tumor Necrosis Factor-alpha
  • Interleukin-6
  • Carbon Dioxide
  • Cyclooxygenase 2
  • Benzaldehydes

Grants and funding

This research was supported by the National Research Foundation of Korea (NRF), a grant funded by the Korean government (MSIT) (No. 2022R1C1C1005770 and 2019R1I1A3A01061885) and by Bio&Medical Technology Development Program of the National Research Foundation (NRF) (No. RS-2023-00236157), and by grants from the Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea.