Curcumin-Containing polyphosphazene nanodrug for Anti-Inflammation and nerve regeneration to improve functional recovery after spinal cord injury

Int J Pharm. 2023 Jul 25:642:123197. doi: 10.1016/j.ijpharm.2023.123197. Epub 2023 Jul 4.

Abstract

The microenvironment of excessive inflammation and the activation of apoptotic signals are primary barriers to neurological recovery following spinal cord injury (SCI). Thus, long-lasting anti-inflammation has become an effective strategy to navigate SCI. Herein, a curcumin (CUR)-containing nanosystem (FCTHPC) with high drug loading efficiency was reported via assembling hydrophobic CUR into cross-linked polyphosphazene (PPZ), and simultaneous loading and coordinating with porous bimetallic polymers for greatly enhanced the water-solubility and biocompatibility of CUR. The nanosystem is noncytotoxic when directing its biological activities. By inhibiting the expression of pro-inflammatory factors (IL-1β, TNF-α and IL-6) and apoptotic proteins (C-caspase-3 and Bax/Bcl-2), which may be accomplished by activating the Wnt/β-catenin pathway, the versatile FCTHPC can significantly alleviate the damage to tissues and cells caused by inflammation and apoptosis in the early stage of SCI. In addition, the long-term in vivo studies had demonstrated that FCTHPC could effectively inhibit the formation of glial scars, and simultaneously promote nerve regeneration and myelination, leading to significant recovery of spinal cord function. This study emphasises the promise of the biocompatible CUR-based nanosystem and provides a fresh approach to effectively treat SCI.

Keywords: Biocompatibility; Cross-linked polyphosphazene; Curcumin; Inflammatory response; Neuroregeneration; Spinal cord injury.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / metabolism
  • Apoptosis
  • Curcumin* / metabolism
  • Curcumin* / pharmacology
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Nanoparticles* / therapeutic use
  • Nerve Regeneration
  • Polymers / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord / metabolism
  • Spinal Cord Injuries* / drug therapy

Substances

  • Curcumin
  • poly(phosphazene)
  • Anti-Inflammatory Agents
  • Polymers