In vivo retention and bioactivity of IL-1ra microspheres in the rat intervertebral disc: a preliminary investigation.
In vivo retention and bioactivity of IL-1ra microspheres in the rat intervertebral disc: a preliminary investigation.
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DOI：
10.1186/s40634-014-0015-8
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发表时间：
2014-12
影响因子：
1.8
通讯作者：
Smith LJ
中科院分区：
文献类型：
--
作者：
Gorth DJ;Martin JT;Dodge GR;Elliott DM;Malhotra NR;Mauck RL;Smith LJ
白介素 1 β (IL-1β) 等炎症细胞因子会促进椎间盘退变的进展。此前，我们在体外证明，通过从聚乳酸共乙醇酸 (PLGA) 微球中递送白介素 1 受体拮抗剂 (IL-1ra)，我们可以在长达 20 天的时间内减弱 IL-1β 对髓核 (NP) 的降解作用。本研究的目的是初步研究微球是否可以在体内成功递送至椎间盘并保留在椎间盘中，以及从这些微球中释放的IL-1ra是否仍具有生物活性。为了进行保留研究，将荧光标记的微球递送至大鼠尾椎间盘的纳米粒子。在长达 56 天的时间点处死大鼠，并使用荧光显微镜定位微球。为了研究IL-1ra微球是否能够在体内有效抑制IL-1β的作用，将四个椎间盘水平分配给以下治疗组：完整；盐水; IL-1β；或IL-1β + IL-1ra微球。 7天后处死大鼠并测量NP糖胺聚糖含量。在长达 28 天的所有时间点，椎间盘中均可见微球，并且定位于 NP、纤维环 (AF) 或两者。单独注射 IL-1β 的椎间盘的糖胺聚糖含量显着低于完整对照。对于注射了 IL-1β 和 IL-1ra 微球的椎间盘，糖胺聚糖含量与完整对照没有显着差异。微球可以成功地在体内递送至椎间盘并保留临床相关的时间范围。微球释放的IL-1ra可有效阻止IL-1β诱导的体内NP糖胺聚糖损失。
Inflammatory cytokines such as interleukin-1 beta (IL-1β) contribute to the progression of intervertebral disc degeneration. Previously we demonstrated, in vitro, that by delivering interleukin-1 receptor antagonist (IL-1ra) from poly(lactic co-glycolic acid) (PLGA) microspheres, we could attenuate the degradative effects of IL-1β on the nucleus pulposus (NP) for up to 20 days. The objective of this study was to undertake a preliminary investigation into whether microspheres could be successfully delivered to and retained in the disc in vivo, and whether IL-1ra released from those microspheres remained biologically active. For retention studies, fluorescently-labeled microspheres were delivered to the NPs of rat caudal discs. Rats were sacrificed at time points up to 56 days, and microspheres were localized using fluorescent microscopy. To investigate whether IL-1ra microspheres could effectively inhibit the effects of IL-1β in vivo, four disc levels were allocated to the following treatment groups: intact; saline; IL-1β; or IL-1β + IL-1ra microspheres. Rats were sacrificed after seven days and NP glycosaminoglycan content was measured. Microspheres were visible in the disc at all time points up to 28 days, and localized to the NP, the annulus fibrosus (AF), or both. Glycosaminoglycan content for discs injected with IL-1β alone was significantly lower than for intact controls. For discs injected with IL-1β along with IL-1ra microspheres, glycosaminoglycan content was not significantly different from intact controls. Microspheres can successfully be delivered to the disc in vivo and retained for a clinically relevant time frame. IL-1ra released from microspheres can effectively prevent IL-1β-induced NP glycosaminoglycan loss in vivo.