pH-Responsive Delivery of H2 through Ammonia Borane-Loaded Hollow Polydopamine for Intervertebral Disc Degeneration Therapy

Abstract

An imbalance in oxidative and inflammatory regulation is the main contributor to intervertebral disc degeneration (IDD). Hydrogen (H2) therapy is a promising antioxidation and anti-inflammatory approach. However, the key to the treatment is how to maintain the long-term effective H2 concentration in the intervertebral disc (IVD). Therefore, we developed a pH-responsive delivery of H2 through ammonia borane-loaded hollow polydopamine (AB@HPDA) for IDD therapy, which has sufficient capacity to control long-term H2 release in an acid-dependent manner in degenerative IVD. The characterization, toxicity, and pH-responsive H2 release of AB@HPDA was detected in vitro. The metabolization of AB@HPDA in the degenerated IVD was tested by in vivo imaging. The therapeutic effect of AB@HPDA on IDD was tested in vivo by X-ray, MRI, water content of the disc, and histological changes. Nuclear extracellular matrix (ECM) components, oxidative stress, and inflammation were also tested to explore potential therapeutic mechanisms. AB@HPDA has good biocompatibility at concentrations less than 500 μg/mL. The H2 release of AB@HPDA was pH responsive. Therefore, AB@HPDAs can provide efficient hydrogen therapy with controlled H2 release in response to the acidic degenerated IVD microenvironment. The metabolization of AB@HPDA in IVD was slow and lasted up to 11 days. HPDA and AB@HPDA significantly inhibited IDD, as tested by X-ray, MRI, disc water content, and histology ( P < 0.05 ). pH-responsive H2 delivery through AB@HPDAs has the potential to efficiently treat IDD by inhibiting ECM degradation and rebalancing oxidative stress and inflammation in degenerative IVDs.

Stimuli-Responsive Delivery Systems for Intervertebral Disc Degeneration

“…This specially designed complex, called AB@HPDA, is characterized by a large surface area, high biocompatibility, and permeability. 112 The complex is incorporated into the nanoparticles and can be injected at degenerated positions. In vivo experiments showed that this injectable nanoparticle significantly reduced tissue oxidative damage by the pH-responsive delivery of H 2 and restored normal physiological functions.…”

“…In vivo experiments showed that this injectable nanoparticle significantly reduced tissue oxidative damage by the pH-responsive delivery of H 2 and restored normal physiological functions. 112 …”