In situ delivery of a curcumin-loaded dynamic hydrogel for the treatment of chronic peripheral neuropathy

J Control Release, 2023 · DOI: 10.1016/j.jconrel.2023.04.002 · Published: May 1, 2023

Simple Explanation

This study explores a new way to treat chronic nerve pain using a special gel that releases a medicine called curcumin. The gel is designed to stick around the injured nerves for a while, helping to reduce inflammation and protect the nerves. The researchers tested this gel on mice with nerve injuries and found that it helped to reduce pain and improve their ability to walk. This is because the gel helps to calm down the inflammation in the nerves and spinal cord, which are major causes of nerve pain. Overall, this study suggests that using this curcumin-releasing gel could be a promising way to help people who have nerve pain after surgery.

Study Duration

3 weeks

Participants

Nine-week-old, male C57BL/6 mice

Evidence Level

Not specified

Key Findings

1
The Gel-Cur-M exhibited superior functions compared to Gel and Cur-M alone, which includes ameliorating hyperalgesia while simultaneously improving locomotor and muscular functions after the nerve injury.
2
Gel-Cur-M also showed extended beneficial effects for preventing the overexpression of TRPV1 as well as microglial activation in the lumbar dorsal root ganglion and spinal cord, respectively, which also contributed to its analgesic effects.
3
orthotopic treatment of Gel-Cur-M regulated in situ inflammation and oxidative stress, protected nerve structure, and further attenuated neuroinflammation as well as neuronal sensitization in both the peripheral and central nervous systems

Research Summary

The study introduces an injectable hydrogel, Gel-Cur-M, loaded with curcumin micelles for treating chronic peripheral neuropathy in mice with chronic constriction injuries (CCI). Gel-Cur-M demonstrated sustained curcumin release at the injury site for at least 21 days, superior pain relief, and improved locomotor and muscular functions compared to Gel or Cur-M alone. The therapeutic effects of Gel-Cur-M involve reducing local inflammation and oxidative stress, protecting nerve structure, and attenuating neuroinflammation and neuronal sensitization in the peripheral and central nervous systems.

Practical Implications

Therapeutic Strategy

Orthotopic injection of Gel-Cur-M is a promising therapeutic strategy that especially benefits patients with peripheral neuropathy who require surgical interventions.

Local Drug Delivery

Local drug delivery is an efficient approach for drugs with poor aqueous solubility (e.g., Cur) to achieve a sufficient drug concentration.

Prevention of Nerve Damage

The Gel-Cur-M hydrogel developed in our study not only showed a promising analgesic effect after peripheral nerve injuries but also protected nerves from chronic damage

Study Limitations

1
The CCI model caused a much milder damage to the nerve than other acute nerve injury models, such as crush injury and nerve transection, so the CCI had limited effects on the downstream innervated muscles.
2
Effects of Cur-M were less significant and effective compared to the hydrogel groups, which could be a result of a rapid clearance of Cur-M after the injection around the nerve.
3
Gel alone may not be effective for the initial induction of inflammation and TRPV1 activation after the nerve injury, but it showed a delayed pain relief in following weeks.

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