• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文会议>World biomaterials congress >Stability and release of two peptides in a novel peptide-based drugs for local intra-articular purpose in osteoarthritis
【24h】

Stability and release of two peptides in a novel peptide-based drugs for local intra-articular purpose in osteoarthritis

机译：在骨关节炎局部关节炎的新型肽类药物中两种肽的稳定性和释放

获取原文
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Introduction: Knee osteothritis (OA) is a leading cause of disability in older adults, research into the specific therapies of OA, is a priority in health sciences. In this project a novel peptide-based nanoparticles (NPs) are proposed to satisfy an unmet clinical need; sustained drug delivery to the knee joint. The objective is to develop a delivery system R- 954 from nanogels hyaluronic acid (HA) /chitosan (CH), either by encapsulation (without covalent bond), or by grafting to the HA (with covalent bond). The peptide r9S4 is an antagonist of the bradykinin receptor (BKB1R) and BQ123 is an antagonist of the endothelin receptor (ETA-R). Kaufman et al. and Moldovan et al. showed that both endotelin-1 (ET-1) and bradykinin play crucial role in vivo in OA pathophysiology, through their catabolic functions in cartilage degradation and inflammation involving metalloproteases MMPs (MMP1-and MMP-13), nitric oxide (NO), and prostaglandins (PGE2). Hyaluronic acid and chitosan based nanohydrogels were chosen as carriers for the two peptides because they could provide an enhanced protection against biochemical aggression and sustained release. Materials and Methods: In the first part, the peptide coupling of the r954 petide and hyaluronic acid (HA) was carried out. The conjugation of the peptide to HA was performed using the well established coupling chemistry of pH sensitive linkers. The carboxylic and primary amine groups present on the peptides allow for simple ligation. To quantify the release and stability of this novel peptide-based drug, a fast and accurate liquid chromatography -tandem mass spectrometry (LC-MS/MS) method was developed. In this method the proteins of the HSF are simply precipitated with acetonitrile, the sample is diluted with mobile phase and injected directly without further purification steps. The method was validated according to the EMA guideline on bioanalytical method validation. Results and discusssion: Peptide release and degradation kinetics study of the coupled composite in human synovlal fluid (HSF) and buffer solutions. We found that a 23% of r954 was released in hsf from the coupled composite in 77 hrs, it means in 39 days the total release. However the release of the peptide bq123 under the same conditions takes a very long time. The degradation kinetics of the peptide r954 and bq123 in the physiological matrix human synovial fluid and under various pH conditions were investigated. The stability testing of the peptide r954 was carry out to provide evidence on how the quality of the drug substance varies with time under the influence of the temperature. When r9S4 was incubated in hsf at 37 °C, was stable during the first 77 hrs. Conclusion: Results are very encouraging and show that the vectorization strategy is feasible. The main perspective: Synthesize sterile synthetic nanogels containing both peptides (encapsulated or grafted) to assess the cytotoxicity and the effects on human cartilage.
机译：介绍：膝关节骨炎（OA）是老年人残疾的主要原因，研究OA的具体疗法，是健康科学的优先事项。在该项目中，提出了一种新的肽基纳米颗粒（NPS）以满足未满足的临床需求;持续的药物输送到膝关节。该目的是通过封装（无共价键）或通过嫁接到HA（具有共价键）来开发来自纳米凝胶透明质酸（HA）/壳聚糖（CH）的递送系统R-954。肽R9S4是Bradykinin受体（BKB1R）的拮抗剂，BQ123是内皮素受体（ETA-R）的拮抗剂。 Kaufman等人。和摩尔多瓦等。表明，通过包裹物质降解和涉及金属蛋白酶MMP（MMP1和MMP-13），一氧化氮（MMP1和MMP-13），一氧化氮（MMP1和MMP-13），氧化氮（NO），和前列腺素（PGE2）。透明质酸和壳聚糖基纳米水凝胶被选择为两种肽的载体，因为它们可以提供增强的生物化学侵蚀和持续释放的保护。材料和方法：在第一部分中，进行R954流化物和透明质酸（HA）的肽偶联。使用良好的pH敏感接头的良好的偶联化学进行肽与HA的缀合。存在于肽上的羧酸和伯胺基团允许简单的连接。为了量化这种新型肽类药物的释放和稳定性，开发了一种快速和精确的液相色谱 - 用于质谱（LC-MS / MS）方法。在该方法中，HSF的蛋白质通过乙腈沉淀出来，将样品用流动相稀释并直接注射，无需进一步纯化步骤。根据生物分析方法验证的EMA指南验证该方法。结果与探讨：人体滑液（HSF）和缓冲溶液偶联复合材料的肽释放与降解动力学研究。我们发现，在77小时的偶联复合材料中，23％的R954在HSF中释放，意味着在39天内释放。然而，在相同条件下肽BQ123的释放需要很长时间。研究了肽R954和BQ123在生理基质人类滑液和各种pH条件下的降解动力学。肽R954的稳定性试验进行了有关药物质量如何随温度的影响而变化的证据。当在37℃的HSF中在37℃温育R9S4时，在前77小时内稳定。结论：结果非常令人鼓舞，表明矢量化策略是可行的。主要观点：合成含有肽（包封或接枝）的无菌合成纳米凝胶，以评估细胞毒性和对人类软骨的影响。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号