• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Acta biomaterialia >Cartilage penetrating cationic peptide carriers for applications in drug delivery to avascular negatively charged tissues
【24h】

Cartilage penetrating cationic peptide carriers for applications in drug delivery to avascular negatively charged tissues

机译：软骨穿透阳离子肽载体，用于药物递送的应用，以腺体带负电的组织

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Drug delivery to avascular, negatively charged tissues like cartilage remains a challenge. The constant turnover of synovial fluid results in short residence time of administered drugs in the joint space and the dense negatively charged matrix of cartilage hinders their diffusive transport. Drugs are, therefore, unable to reach their cell and matrix targets in sufficient doses, and fail to elicit relevant biological response, which has led to unsuccessful clinical trials. The high negative fixed charge density (FCD) of cartilage, however, can be used to convert cartilage from a barrier to drug entry into a depot by making drugs positively charged. Here we design cartilage penetrating and binding cationic peptide carriers (CPCs) with varying net charge, spatial distribution and hydrophobicity to deliver large-sized therapeutics and investigate their electro-diffusive transport in healthy and arthritic cartilage. We showed that CPC uptake increased with increasing net charge up to +14 but dropped as charge increased further due to stronger binding interactions that hindered CPC penetrability and uptake showing that weak reversible binding is key to enable their penetration through full tissue thickness. Even after 90% GAG depletion, while CPC +14 uptake reduced by over 50% but still had a significantly high value of 148x showing that intra-tissue long-range charge-based binding is further stabilized by short-range H-bond and hydrophobic interactions. The work presents an approach for rational design of cationic carriers based on tissue FCD and properties of macromolecules to be delivered. These design rules can be extended to drug delivery for other avascular, negatively charged tissues.
机译：药物递送给养血管，带负电荷的组织如软骨仍然是一个挑战。滑膜流体的不断变化导致关节空间中药物的速度短暂的停留时间，并且软骨带负电荷的基质阻碍了它们的扩散运输。因此，药物不能以足够的剂量达到其细胞和基质靶标，并且未能引发相关的生物反应，这导致了不成功的临床试验。然而，软骨的高负固定电荷密度（FCD）可用于通过使药物带正电荷的药物将软骨转化为药物进入仓库。在这里，我们设计了具有不同净充电，空间分布和疏水性的软骨渗透和结合阳离子肽载体（CPC），以提供大型治疗方法，并在健康和关节炎软骨中调查它们的电漫射运输。我们表明，由于较强的结合相互作用，随着CPC可渗透性和摄取的较弱，液化相互作用，CPC摄取增加，但由于充满了弱的可逆结合，因此CPC摄取增加，但由于较强的结合相互作用，其较强的结合相互作用，呈较强的结合相互作用。显示弱可逆结合是通过完全组织厚度来渗透来实现它们的钥匙。即使在90％gag耗尽后，CPC +14摄取量也减少了超过50％，但仍然具有显着高的148倍，表明通过短范围的H键和疏水性进一步稳定组织的长距离电荷的结合互动。该工作提出了一种基于组织FCD和待交付大分子的阳离子载体的合理设计方法。这些设计规则可以扩展到其他养血管的药物递送，带负电荷的组织。

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