用于体外循环管材的新型醛基化海藻酸钠-地塞米松缓释涂层研究

Research on a Novel Sodium Alginate-Dexamethasone Composite Coating with Multi-Aldehyde Groups Applied to Extracoporeal Circuits

研制新型醛基化海藻酸钠-地塞米松缓释涂层,筛选最佳涂层模式和涂层条件,对涂层稳定性、抗凝性能、缓释性能等进行评价。高碘酸钠氧化海藻酸钠得醛基化海藻酸钠(OSA),酸化预处理聚氯乙烯(PVC)管材表面,聚乙烯亚胺涂抹经酸化预处理的PVC管材。聚乙烯亚胺涂层管材(PP)通过离子键直接交联地塞米松磷酸钠(DSP)制备DSP单涂层管材(PPD组),PP通过离子键交联(PPI组)、共价键交联(PPC组)两种方式制备醛基化海藻酸钠-地塞米松磷酸钠复合涂层管材,同时设置空白对照(C组)。以正交实验筛选3种涂层模式的最佳涂层条件。对3种涂层管材进行涂层物定性和定量分析,抗凝、抗血小板、抗蛋白粘附、体外释放等性能进行评价研究,从而筛选最佳涂层模式。结果显示,PPD、PPI和PPC等3种涂层模式均能固定DSP,最佳固定密度分别为(3.33±0.75)、(1.63±0.76)、(2.06±0.68)μg/cm2;复合涂层组(PPI和PPC)血小板粘附量(109/L)分别为(13.88±1.89)和(19.13±3.40),均较C组(41.38±3.20)显著减少;复合涂层组蛋白粘附量(mg/cm2)(HAS:(29.86±13.57)和(46.67±3.20),HPF:(34.99±3.52)和(45.67±3.79)),均较PPD组(HAS:(68.73±4.26),HPF:(72.54±7.90))显著减少;体外释放方面PPC组明显优于PPI组。醛基化海藻酸钠-地塞米松复合涂层具备良好的血液相容性和生物相容性,通过共价交联的DSP能够达到缓释效果。

The aim of this work is to prepare a novel composite coating of sodium alginate and dexamethasone. By optimizing the coating mode and conditions, the properties of stability, anticoagulation and controlled release were evaluated. Polyethyleneimine （PEI） was coated on PVC pipelines surface pretreated with acidification, dexamethasone sodium phosphate （DSP） was coated on PEI-coated pipelines （PP） with ionic bond, DSP coated pipelines were created （ Group PPD）. Pipelines coated OSA-DXM composite were created by ionic bond （Group PPI） or covalent bond （Group PPC ）. The control group （Group C ） was set as well. The optimum coating condition was obtained by the orthogonal test. By evaluating the properties of different coated pipelines including anticoagulation, platelet adhesion, protein adhesion and release in vitro, the optimum coating mode was determined. DSP can be bound to PVC surface in Group PPD, PPI and PPC. The optimum immobilization quantity of DSP on different groups are （3.33 ± 0. 75 ） , （ 1.63 ± 0.76）, （2.06 ± 0. 68 ） μg/cm2. The platelet adhesion （109/L） of Group PPI and PPC （13.88 ± 1.89 and 19.13 ± 3.40 ） was significantly reduced than that of Group C （41.38 ±3.20）. The protein adhesion （mg/cm2） of Group PPI and PPC （ HAS： 29. 86 ±13.57 and 46.67 ± 3.20, HPF： 34.99 ± 3.52 and 45.67 ± 3.79） was significantly decreased than that of Group PPD （Has： 68.73 ± g. 26, HPF： 72. 54 ± 7.90）. The release property of Group PPC is superior to that of Group PPI. The coating of OSA-DXM composite exhibited improved hemocompatibility. Covalently bound DSP can be controlled released.