Minocycline-Loaded Poly(α-Lipoic Acid)–Methylprednisolone Prodrug Nanoparticles for the Combined Anti-Inflammatory Treatment of Spinal Cord Injury

Abstract

Purpose Traumatic spinal cord injury (TSCI) induces a powerful inflammatory response that can significantly exacerbate the extent and severity of neural damage (termed as “secondary injury”). Thus, the suppression of inflammation is crucial for reducing neurological dysfunction following TSCI. However, the conventional anti-inflammatory drugs show limited efficacy because of poor penetration and release kinetics at the injury site. This study describes the design, synthesis, release kinetics, biosafety, and preclinical efficacy of minocycline (MC)-loaded poly(α-lipoic acid)–methylprednisolone (PαLA-MP) prodrug nanoparticles (NPs) for the combined anti-inflammatory treatment of TSCI. Methods NPs were produced by conjugating MP to PαLA and then loading MC. The NP structure was confirmed through 1 H nuclear magnetic resonance ( 1 H NMR), Fourier transform infrared spectroscopy, ultraviolet–visible absorption spectroscopy, gel permeation chromatography, dynamic light scattering, and transmission electron microscopy. Drug-loading content and efficacy were measured using high-performance liquid chromatography (HPLC) or 1 H NMR and release kinetics through HPLC. Biosafety was examined using the MTT assay, cell penetration efficiency using confocal microscopy, and flow cytometry using Cyanine5 (Cy5)-labeled MC-PαLA-MP NPs, effects on injury-induced pro-inflammatory cytokine release using enzyme-linked immunosorbent assays and immunofluorescence, and treatment efficacy by measuring motor recovery in a rat model of TSCI. Results The MC-PαLA-MP NPs exhibited high biocompatibility and released 81% MC and 54% MP within 24 h under TSCI-like conditions, effectively reducing 40% of pro-inflammatory cytokine release both in cultures and injured rat spinal cord tissues. Systemic injection increased the Basso, Beattie, Bresnahan score of TSCI rats from 2.33 ± 0.52 to 8.83 ± 1.83 in 8 weeks, providing effective neuroprotection and enhanced exercise recovery in the TSCI rats. Conclusion The MC-PαLA-MP NPs can mitigate secondary inflammation and preserve motor function following experimental TSCI, which suggests their potential for clinical application.

Epigallocatechin-3-gallate selenium nanoparticles for neuroprotection by scavenging reactive oxygen species and reducing inflammation

“…The therapeutic concentration for MP is the clinically recommended therapeutic concentration for spinal cord injury ( Ahuja et al, 2017b ; Zhang et al, 2018 ). MP is one of most frequently used drug for clinical treatment of SCI, which has been routinely established as a control group in animal studies ( Huang et al, 2020 ; Lin et al, 2022 ). The BBB score of rats treated with 10 mg/kg EGCG-Se NP (8.4 ± 0.5) was significantly better than that of the saline group (3.2 ± 0.4) at 8 weeks after surgery ( Figure 4A ).…”

“…SY202103013). We used the weight-drop SCI model ( Lin et al, 2022 ). In simple terms, rats were deeply anaesthetized with pentobarbitone sodium, and thoracic laminectomy was performed at the T10 level.…”

Encapsulation of Selenium Nanoparticles and Metformin in Macrophage-Derived Cell Membranes for the Treatment of Spinal Cord Injury

“…SCI can severely reduce the quality of life of patients and place a significant financial burden on their families. The focus of current research is to obtain effective drugs for the treatment of SCI. , However, these drugs are still unable to cross the BSCB by themselves and lack the ability to target the lesion area, resulting in unsatisfactory clinical efficacy. As a trace element, selenium plays an important role in SCI by regulating enzyme activity and thus scavenging excess ROS.…”

Carrier-Free Nanodrug Based on Co-Assembly of Methylprednisolone Dimer and Rutin for Combined Treatment of Spinal Cord Injury

“…The rat SCI model was prepared as in a previous report. 48 Female Sprague−Dawley rats were anesthetized by pentobarbital sodium, and the T10 segment laminectomy was removed to expose the spinal cord. The dorsal surface of the spinal cord was hit by a 40 g rod dropped from a height of 6 cm.…”

“…The rat SCI model was prepared as in a previous report . Female Sprague–Dawley rats were anesthetized by pentobarbital sodium, and the T10 segment laminectomy was removed to expose the spinal cord.…”