Microparticles Locally Deliver Active Interleukin‐1 Receptor Antagonist In Vivo,Advanced Healthcare Materials

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Microparticles Locally Deliver Active Interleukin‐1 Receptor Antagonist In Vivo
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2018-07-04 , DOI: 10.1002/adhm.201800263
Anna E. B. Clements ₁ , Emily R. Groves ₁ , Connie S. Chamberlain ₁ , Ray Vanderby ₁ , William L. Murphy ₁

Affiliation

Despite significant research in therapeutic protein delivery, localized and sustained delivery of active therapeutic proteins remains a challenge. Delivery is a particular challenge for therapeutic proteins with a short half‐life. Herein, localized delivery of interleukin‐1 receptor antagonist (IL‐1Ra) by mineral coated microparticles (MPs) is assessed in a healing rat medial collateral ligament (MCL). The local tissue concentration and systemic serum concentration of IL‐1Ra, the anti‐inflammatory activity of IL‐1Ra delivered with MPs, and whether IL‐1Ra loaded MPs (IL‐1Ra MPs) are immunogenic in a healing ligament are also examined. IL‐1Ra MPs significantly increase the local concentration of IL‐1Ra compared to soluble IL‐1Ra at 7 and 14 days after treatment but do not elevate the systemic concentration of IL‐1Ra at these time points, indicating localized delivery of IL‐1Ra. IL‐1Ra MPs significantly reduce inflammation caused by the MPs themselves, indicating the IL‐1Ra is active. Finally, IL‐1Ra MPs do not induce a foreign body response and decrease the immunogenicity of human IL‐1Ra in a healing rat MCL. Overall, mineral coated microparticles have the ability to locally deliver active therapeutic proteins for an extended period of time.

中文翻译：

微粒在体内局部递送活性白介素-1受体拮抗剂

尽管在治疗性蛋白质递送方面进行了大量研究，但是活性治疗性蛋白质的局部和持续递送仍然是一个挑战。对于半衰期短的治疗性蛋白质，递送是一个特殊的挑战。本文中，在愈合的大鼠内侧副韧带（MCL）中评估了矿物质包被的微粒（MPs）对白介素-1受体拮抗剂（IL-1Ra）的局部递送。还检查了IL-1Ra的局部组织浓度和全身血清浓度，MPs递送的IL-1Ra的抗炎活性以及负载IL-1Ra的MPs（IL-1Ra MPs）在愈合韧带中是否具有免疫原性。与可溶性IL-1Ra在治疗后7天和14天相比，IL-1Ra MP显着增加了IL-1Ra的局部浓度，但在这些时间点并未提高IL-1Ra的全身浓度，表示IL-1Ra的局部递送。IL-1Ra MP可以显着减少MP本身引起的炎症，表明IL-1Ra是活跃的。最后，IL-1Ra MP在康复的大鼠MCL中不会诱导异物应答并降低人IL-1Ra的免疫原性。总体而言，矿物包被的微粒具有在较长时间内局部递送活性治疗性蛋白质的能力。

更新日期：2018-07-04

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