Anti-inflammatory Surface Coatings Based on Polyelectrolyte Multilayers of Heparin and Polycationic Nanoparticles of Naproxen-Bearing Polymeric Drugs
Anti-inflammatory Surface Coatings Based on Polyelectrolyte Multilayers of Heparin and Polycationic Nanoparticles of Naproxen-Bearing Polymeric Drugs
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DOI：
10.1021/acs.biomac.9b01098
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发表时间：
2019-10-01
影响因子：
6.2
通讯作者：
Groth, Thomas
中科院分区：
文献类型：
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作者：
Al-Khoury, Hala;Espinosa-Cano, Eva;Groth, Thomas
对生物材料的免疫反应可产生慢性炎症和纤维化，导致植入失败，这与生物材料的表面特性有关。本工作描述了聚电解质多层（PEM）涂层的制备和表征，该涂层结合了肝素作为聚阴离子的抗炎活性和萘普生的潜在释放，萘普生是一种非甾体抗炎药，从具有阳离子表面电荷的聚合物纳米颗粒（NP）中释放。用物理方法对聚电解质多层进行了表征，以估计多层的生长、厚度、zeta电位和形貌。研究发现，具有NP的多层膜具有负zeta电位并表现出粘弹性行为，而形貌研究表明纳米颗粒形成连续的表面涂层。用thp -1来源的巨噬细胞研究短期抗炎活性（时间尺度为48 h），结果表明，与多层形成的聚阴离子聚苯乙烯磺酸相比，含有肝素的PEM降低了细胞粘附和il -1- β的分泌。另一方面，与含有壳聚糖作为替代多阳离子的PEM相比，PEM中NP的存在与15天后异物巨细胞形成减少有关，这表明含有萘普生的纳米颗粒具有长期的抗炎作用。研究还表明，巨噬细胞能够从多层膜中吸收NP，这表明溶酶体腔室中NP的消化释放了萘普生。这些结果表明，由肝素和萘普生基NP组成的生物传感器植入物表面涂层有可能减轻植入后的异物反应，从而改善植入物的长期功能。
Immune response to biomaterials can produce chronic inflammation and fibrosis leading to implant failure, which is related to the surface properties of the biomaterials. This work describes the preparation and characterization of polyelectrolyte multilayer (PEM) coatings that combine the anti-inflammatory activity of heparin as polyanion with the potential release of Naproxen, a nonsteroidal anti-inflammatory drug from polymeric nanoparticles (NP) with cationic surface charge. The polyelectrolyte multilayers were characterized by physical methods to estimate multilayer growth, thickness, zeta potential, and topography. It was found that multilayers with NP had negative zeta potentials and expressed a viscoelastic behavior, while studies of topography showed that nanoparticles formed continuous surface coatings. THP-1-derived macrophages were used to study short-term anti-inflammatory activity (time scale 48 h), showing that PEM that contained heparin reduced cell adhesion and IL1-beta secretion, when compared to those with polystyrenesulfonate, used as alternative polyanion in multilayer formation. On the other hand, the presence of NP in PEM was related to a reduced foreign body giant cell formation after 15 days, when compared to PEM that contained chitosan as alternative polycation, which suggests a long-term anti-inflammatory effect of Naproxen-containing nanoparticles. It was also shown that macrophages were able to take up NP from multilayers, which indicates a release of Naproxen by digestion of NP in the lysosomal compartment. These findings indicate that surface coatings composed of heparin and Naproxen-based NP on implants such as biosensors have the potential to attenuate foreign body reaction after implantation, which may improve the long-term functionality of implants.