Local delivery of minocycline from metal ion-assisted self- assembled complexes promotes neuroprotection and functional recovery after spinal cord injury

Biomaterials, 2017 · DOI: 10.1016/j.biomaterials.2016.10.002 · Published: January 1, 2017

Simple Explanation

Spinal cord injuries lead to secondary damage, and current treatments often target only a few injury mechanisms. Minocycline is a drug that can address many of these mechanisms, but it needs to be delivered in high concentrations. The problem is that high doses cause toxicity. Researchers have developed a hydrogel system that uses metal ions to create complexes that release minocycline in a controlled way. This system can be injected locally, delivering a sufficient dose of minocycline without causing additional damage. The study found that local delivery of minocycline, even at lower doses than typically used in humans, was more effective in reducing secondary injury and improving motor function compared to injecting high doses of minocycline systemically.

Study Duration

6 Weeks

Participants

Female Sprague-Dawley rats (250–300 g)

Evidence Level

Not specified

Key Findings

1
Local delivery of MH at a dose of 1.3 mg/kg generated significantly higher MH concentration in the local spinal cord tissue than intraperitoneal (IP) injection of 495 mg/kg MH over 5 days.
2
Local MH gel treatment significantly decreased the total lesion volume by 58.5% compared to untreated control, whereas IP injection only decreased lesion volume by 29.8%.
3
Local MH gel treatment significantly improved FLS and grid walking scores compared to untreated control and blank gel groups over the time course of 1–6 weeks after injury.

Research Summary

The study introduces a novel drug delivery system for minocycline (MH) using metal ion-assisted self-assembled complexes within a hydrogel, designed for local intrathecal administration to treat spinal cord injury (SCI). The key finding is that local delivery of MH, even at lower doses than systemic administration, results in higher MH concentrations in the spinal cord tissue and leads to superior neuroprotection and functional recovery in a rat SCI model. The authors conclude that this drug delivery system holds great therapeutic potential for SCI treatment and potentially other neurological disorders due to its ability to safely deliver high concentrations of MH locally.

Practical Implications

Improved SCI Treatment

The developed drug delivery system offers a more effective and safer method for delivering minocycline to treat spinal cord injuries.

Broad Applicability

The technology can be adapted for treating other neurological disorders where local delivery of high drug concentrations is needed.

Clinical Translation

The use of biocompatible materials and a clinically relevant delivery route increases the potential for translation to human clinical trials.

Study Limitations

1
Further increasing the dose of local MH treatment within the first 7 days after SCI would be more effective in promoting neuroprotection, which warrants further investigation.
2
The interplay among the four factors (drug loading, DS/MH ration, Mg2+ concentration, and adding chitosan) that modulate MH release is complex.
3
MH concentration in the local spinal cord tissue was lower than the fully neuroprotective level of 35 μg/mL at day 3 and 7 after MH gel administration.

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