Intra-articular injection of kartogenin-conjugated polyurethane nanoparticles attenuates the progression of osteoarthritis.
Intra-articular injection of kartogenin-conjugated polyurethane nanoparticles attenuates the progression of osteoarthritis.
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关节内注射卡托根配基聚氨酯纳米粒子可减缓骨关节炎的进展
DOI：
10.1080/10717544.2018.1461279
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发表时间：
2018-11
期刊：
影响因子：
6
通讯作者：
Yan Z
中科院分区：
文献类型：
--
作者：
Fan W;Li J;Yuan L;Chen J;Wang Z;Wang Y;Guo C;Mo X;Yan Z
摘要骨关节炎（OA）是最常见的关节疾病，也是导致肢体残疾的主要原因之一，目前迫切需要减缓OA的进展。关节内注射是治疗关节疾病的有效方法，但其疗效主要取决于药物在关节内的作用时间。给药系统可以提供药物控制释放，减少IA注射次数。在这项研究中，两亲性聚氨酯与侧氨基的合成和酰胺键之间形成聚氨酯的胺基和羧基的kartogenin（KGN），一个小分子的报告，显示再生和保护作用的软骨。结果表明，KGN-聚氨酯纳米粒（PN-KGN）呈球形，平均粒径约为25 nm，具有良好的缓释和控释性能。PN-KGN对软骨细胞无细胞毒性和促炎作用。对OA模型的治疗效果显示，关节腔内注射KGN可减缓OA的进展，但12周时软骨退变明显，出现基质丢失和纵裂。相比之下，即使在12周时，IA注射PN-KGN也显示出更少的软骨变性和显著更低的OARSI评分，表明PN-KGN可以进一步阻止OA的发展。免疫组化也证实，IA注射PN-KGN保留了软骨基质的正常组成，具有更强的Col II染色和更少的Col I染色。总之，IA注射PN-KGN是治疗OA的更好的潜在策略，具有长期的软骨保护和较少的IA注射。
Abstract Osteoarthritis (OA) is the most common form of joint disease and a leading cause of physical disability, there is an urgent need to attenuate the progression of OA. Intra-articular (IA) injection is an effective treatment for joints diseases, however, the therapeutic effects mostly depend on the efficacy of drug duration in joints. Drug delivery system can provide drug-controlled release and reduce the number of IA injection. In this study, amphiphilic polyurethanes with pendant amino group were synthesized and amide bonds were formed between the amine group of polyurethane and the carboxyl group of kartogenin (KGN), a small molecular reported to show both regenerative and protective effects on cartilage. Our results showed that KGN-conjugated polyurethane nanoparticles (PN-KGN) were spherical and regular in shape with an average size of 25 nm and could sustained and controlled release of KGN in vitro. PN-KGN showed no cytotoxicity and pro-inflammatory effects on chondrocytes. The therapeutic effects in OA model showed that IA injection of KGN could attenuate the progress of OA, however, the cartilage degeneration became obviously at 12 weeks with matrix loss and vertical fissures. By contrast, IA injection of PN-KGN showed less cartilage degeneration with significant lower OARSI scores even at 12 weeks, indicating PN-KGN could further arrest the development of OA. Immunohistochemistry also validated that IA injection of PN-KGN retained the normal compositions of cartilage matrix, with much stronger Col II staining and less Col I staining. In conclusion, IA injection of PN-KGN is a better potential strategy to treat OA, with long-time cartilage protection and less IA injections.
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影响因子：
3.7
作者：
Morgen, Michael;Tung, David;Boras, Britton;Miller, Warren;Malfait, Anne-Marie;Tortorella, Micky
通讯作者：
Tortorella, Micky
影响因子：
33.7
作者：
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通讯作者：
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影响因子：
0.1
作者：
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通讯作者：
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影响因子：
9.5
作者：
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通讯作者：
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影响因子：
56.9
作者：
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通讯作者：
Schultz, Peter G.