Introduction

Oxidative stress due to excess reactive oxygen species (ROS) is related to many chronic illnesses including degenerative disc disease and osteoarthritis. MnTnBuOE-2-PyP⁵⁺ (BuOE), a manganese porphyrin analog, is a synthetic superoxide dismutase mimetic that scavenges ROS and has established good treatment efficacy at preventing radiation-induced oxidative damage in healthy cells. BuOE has not been studied in degenerative disc disease applications and only few studies have loaded BuOE into drug delivery systems. The goal of this work is to engineer BuOE microparticles (MPs) as an injectable therapeutic for long-term ROS scavenging.

Methods

Methacrylated chondroitin sulfate-A MPs (vehicle) and BuOE MPs were synthesized via water-in-oil polymerization and the size, surface morphology, encapsulation efficiency and release profile were characterized. To assess long term ROS scavenging of BuOE MPs, superoxide scavenging activity was evaluated over an 84-day time course. In vitro cytocompatibility and cellular uptake were assessed on human intervertebral disc cells.

Results

BuOE MPs were successfully encapsulated in MACS-A MPs and exhibited a slow-release profile over 84 days. BuOE maintained high potency in superoxide scavenging after encapsulation and after 84 days of incubation at 37 °C as compared to naked BuOE. Vehicle and BuOE MPs (100 µg/mL) were non-cytotoxic on nucleus pulposus cells and MPs up to 23 µm were endocytosed.

Conclusions

BuOE MPs can be successfully fabricated and maintain potent superoxide scavenging capabilities up to 84-days. In vitro assessment reveals the vehicle and BuOE MPs are not cytotoxic and can be taken up by cells.

中文翻译：

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将锰卟啉封装在硫酸软骨素-A 微粒中用于长期活性氧清除

介绍

过量活性氧（ROS）引起的氧化应激与许多慢性疾病有关，包括退行性椎间盘疾病和骨关节炎。MnTnBuOE-2-PyP ⁵⁺ (BuOE) 是一种锰卟啉类似物，是一种合成的超氧化物歧化酶模拟物，可清除 ROS，并在预防健康细胞中辐射引起的氧化损伤方面具有良好的治疗效果。BuOE 在退行性椎间盘疾病中的应用尚未得到研究，只有少数研究将 BuOE 加载到药物输送系统中。这项工作的目标是设计 BuOE 微粒 (MP) 作为长期 ROS 清除的注射疗法。

方法

通过油包水聚合合成甲基丙烯酸化硫酸软骨素-A MP（载体）和 BuOE MP ，并对其尺寸、表面形貌、包封效率和释放曲线进行了表征。为了评估 BuOE MP 的长期 ROS 清除能力，在 84 天的时间过程中评估了超氧化物清除活性。在人椎间盘细胞上评估了体外细胞相容性和细胞摄取。

结果

BuOE MP 成功封装在 MACS-A MP 中，并在 84 天内表现出缓慢释放特性。与裸露的 BuOE 相比，BuOE 在封装后以及在 37°C 下孵育 84 天后仍保持高效的超氧化物清除能力。载体和 BuOE MP (100  µ g/mL) 对髓核细胞无细胞毒性，最大 23  µ m 的 MP 被内吞。

结论

BuOE MP 可以成功制造并保持有效的超氧化物清除能力长达 84 天。体外评估表明载体和 BuOE MP 不具有细胞毒性，可以被细胞吸收。