Localised delivery of quercetin by thermo-sensitive PLGA-PEG-PLGA hydrogels for the treatment of brachial plexus avulsion

Abstract

Accumulating evidence indicates that oxidative stress and inflammation are implicated in brachial plexus avulsion (BPA). Quercetin has anti-inflammatory, anti-oxidant, anti-apoptotic, and neuroprotective properties. This study investigated the therapeutic efficacy of a temperature-sensitive poly(D,L-lactide-co-glycolide)-poly(ethylene-glycol)-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) hydrogel sustained-release system of quercetin in BPA. In situ injections of the hydrogel loaded with different concentrations of quercetin were conducted in a rat model of BPA. Significantly reduced reactive oxygen species and interleukin-6 levels in the injured spinal cord 24 h post-surgery, increased number of anterior horn motor and functional neurons in the spinal cord 6 weeks post-surgery, thickened biceps muscle fibres and enlarged endplate area with clear structure, reduced demyelinated peripheral nerves, and significantly increased Terzis grooming test scores were found in the groups with 50 or 100 mg/ mL quercetin-loaded hydrogels compared with the control and blank hydrogel groups. In conclusion, the temperature-sensitive quercetin loaded PLGA-PEG-PLGA hydrogel sustained-release system can alleviate oxidative damage and inflammation in the spinal cord, increase neuron survival rate, and promote nerve regeneration and motor function recovery in rats with early BPA. The findings suggest that this drug-loaded hydrogel has potential applications in the clinical treatment of BPA.

Quercetin: A Bioactive Compound Imparting Cardiovascular and Neuroprotective Benefits: Scope for Exploring Fresh Produce, Their Wastes, and By-Products

“…The results obtained suggested that oxidative damage and inflammation in the spinal cord were improved along with increase neuron survival rate and promotion in nerve regeneration and motor function recovery. The authors suggest that the sustainable approach of quercetin delivery has promising applications in the clinical treatment of brachial plexus avulsion (BPA) [112]. Based on the study carried out by Yu et al [113] the increase in the survival rate of PC12 injured by Aβ25-35, promotion of cell proliferation, and antagonization of the toxicity of Aβ due to quercetin, led it to be considered as a strong agent as a drug candidate for the treatment of Alzheimer disease.…”

Comparison of Different In Vivo Animal Models of Brachial Plexus Avulsion and Its Application in Pain Study

“…Similar rat or mouse models of upper-middle trunk and global trunk avulsion were successively reported to expound the mechanism of motor neuron degeneration and/or to evaluate different repair and reconstruction methods [ 39 – 41 ]. A most recent research of Huang et al [ 42 ] reported that the temperature-sensitive quercetin-loaded PLGA-PEG-PLGA hydrogel sustained-release system could promote nerve regeneration and motor function recovery during the early stage of BPA due to its intrinsic function of anti-inflammation, which had a good prospect from bench to bedside translation. Meanwhile, the posterior approach models also could be used in the field of neuropathic pain research according to recent work.…”

Thermo-sensitive electroactive hydrogel combined with electrical stimulation for repair of spinal cord injury

“…Hydrogel scaffolds also have electrical conductivity and can simulate the electrophysiologic environment of nerve tissue in combination with exogenous ES. Hydrogels have been used for nerve repair through the delivery of small molecule drugs in a rat brachial plexus injury model [13].…”