Prolonged Release and Functionality of Interleukin-10 Encapsulated within PLA-PEG Nanoparticles
Prolonged Release and Functionality of Interleukin-10 Encapsulated within PLA-PEG Nanoparticles
复制标题
DOI：
10.3390/nano9081074
复制
发表时间：
2019-08-01
期刊：
影响因子：
5.3
通讯作者：
Dennis, Vida A.
中科院分区：
文献类型：
--
作者：
Duncan, Skyla A.;Dixit, Saurabh;Dennis, Vida A.
由细胞因子和趋化因子诱导的炎症是衣原体感染的组成部分。据报道，抗炎细胞因子白细胞介素（IL）-10能有效抑制小鼠巨噬细胞中由衣原体引发的炎性细胞因子的分泌。尽管IL-10被用于临床应用，但由于其半衰期短，其治疗用途受到限制。在这里，我们记录了IL-10成功包裹在PLA-PEG（聚乳酸-聚乙二醇）可生物降解聚合物纳米颗粒中，以延长其半衰期。我们的结果显示了包封的IL-10尺寸（类似于238 nm）、ζ电位（-14.2 mV）、多分散指数（0.256）、包封效率（类似于77%）和长达60天的延长的缓慢释放模式。如差示扫描量热法分析所示，交联的IL-10的温度稳定性是有利的，证明了高达89 ° C的热容。包封的IL-10以时间和浓度依赖性方式调节刺激的巨噬细胞中IL-6和IL-12 p40的释放，并差异诱导SOCS1和SOCS3，如由巨噬细胞中的衣原体刺激物诱导的。我们的发现为纯化的IL-10提供了巨大的潜力，不仅用于衣原体炎性疾病，而且还用于生物医学治疗应用。
Inflammation, as induced by the presence of cytokines and chemokines, is an integral part of chlamydial infections. The anti-inflammatory cytokine, interleukin (IL)-10, has been reported to efficiently suppress the secretion of inflammatory cytokines triggered by Chlamydia in mouse macrophages. Though IL-10 is employed in clinical applications, its therapeutic usage is limited due to its short half-life. Here, we document the successful encapsulation of IL-10 within the biodegradable polymeric nanoparticles of PLA-PEG (Poly (lactic acid)-Poly (ethylene glycol), to prolong its half-life. Our results show the encapsulated-IL-10 size (similar to 238 nm), zeta potential (-14.2 mV), polydispersity index (0.256), encapsulation efficiency (similar to 77%), and a prolonged slow release pattern up to 60 days. Temperature stability of encapsulated-IL-10 was favorable, demonstrating a heat capacity of up to 89 degrees C as shown by differential scanning calorimetry analysis. Encapsulated-IL-10 modulated the release of IL-6 and IL-12p40 in stimulated macrophages in a time- and concentration-dependent fashion, and differentially induced SOCS1 and SOCS3 as induced by chlamydial stimulants in macrophages. Our finding offers the tremendous potential for encapsulated-IL-10 not only for chlamydial inflammatory diseases but also biomedical therapeutic applications.