Cartilage-targeting drug delivery: can electrostatic interactions help?
Cartilage-targeting drug delivery: can electrostatic interactions help?
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DOI：
10.1038/nrrheum.2016.210
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发表时间：
2017-03-01
影响因子：
33.7
通讯作者：
Grodzinsky, Alan J.
中科院分区：
文献类型：
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作者：
Bajpayee, Ambika G.;Grodzinsky, Alan J.
目前的关节内药物递送方法不能保证足够的药物渗透到软骨组织中，以达到引起所需生物反应所需的浓度的细胞和基质靶标。在这里，我们提供了我们的观点，利用电荷-电荷（静电）相互作用，以提高药物渗透和运输到软骨，并使持续结合的药物在组织的高度负电荷的细胞外基质。通过将药物与具有最佳尺寸和电荷的带正电荷的纳米载体偶联，软骨可以从药物屏障转化为药物储库，用于持续的组织内递送。或者，多种药物本身可以通过用专门的带正电荷的蛋白质结构域功能化它们来使其穿透软骨。最后，我们强调，适当的动物模型，与软骨厚度类似的人，必须用于研究药物的运输和保留在软骨。
Current intra-articular drug delivery methods do not guarantee sufficient drug penetration into cartilage tissue to reach cell and matrix targets at the concentrations necessary to elicit the desired biological response. Here, we provide our perspective on the utilization of charge-charge (electrostatic) interactions to enhance drug penetration and transport into cartilage, and to enable sustained binding of drugs within the tissue's highly negatively charged extracellular matrix. By coupling drugs to positively charged nanocarriers that have optimal size and charge, cartilage can be converted from a drug barrier into a drug reservoir for sustained intra-tissue delivery. Alternatively, a wide variety of drugs themselves can be made cartilage-penetrating by functionalizing them with specialized positively charged protein domains. Finally, we emphasize that appropriate animal models, with cartilage thickness similar to that of humans, must be used for the study of drug transport and retention in cartilage.