一种二维C3N4纳米片用于水溶性药物丹酚酸B的高负载及缓释作用  

A two-dimensional g-C3N4 nanosheet for high loading and sustained release of water-soluble drug salvianolic acid B

作　　者：梁咏诗 丁陈陈 罗培[4] 张志锋[4] 温露 陈钢 LIANG Yong-shi;DING Chen-chen;LUO Pei;ZHANG Zhi-feng;WEN Lu;CHEN Gang(School of Pharmacy,Guangdong Pharmaceutical University,Guangzhou 510006,China;Guangdong Provincial Key Laboratory of Advanced Drug Delivery,Guangdong Pharmaceutical University,Guangzhou 510006,China;Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System,Guangdong Pharmaceutical University,Guangzhou 510006,China;State Key Laboratory for Quality Research in Chinese Medicines,Macao University of Science and Technology,Macao 000853,China)

机构地区：[1]广东药科大学药学院,广东广州510006 [2]广东药科大学,广东省药物新剂型重点实验室,广东广州510006 [3]广东药科大学,广东省局部精准递药制剂工程技术研究中心,广东广州510006 [4]澳门科技大学,中药质量研究国家重点实验室,中国澳门000853

出　　处：《药学学报》2020年第6期1296-1305,共10页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81773917)。

摘　　要：利用载体输送水溶性药物常存在负载量低及释放迅速的问题,构建一种高负载量的缓释递药系统是水溶性药物临床应用的迫切需要。二维层状纳米材料比表面积高,在药物递送中具有巨大的潜力。本研究由尿素煅烧得到块状氮化碳(bulk graphitic carbon nitride,b-g-C3N4),使用碱化学-超声辅助剥离法制备氮化碳纳米片(graphitic carbon nitride nanosheets,g-C3N4-NS),采用扫描电镜、透射电镜和原子力显微镜考察g-C3N4-NS的形貌特征,X-射线衍射仪和红外光谱解析g-C3N4-NS的结构特征,紫外光谱法和荧光光谱法研究g-C3N4-NS的光学性质,并应用扫描电镜及X-射线衍射仪探究g-C3N4-NS稳定性。利用聚乙烯亚胺(polyethyleneimine,PEI)对g-C3N4-NS进行功能化修饰,以丹酚酸B(salvianolic acid B,Sal B)为水溶性药物模型,探讨g-C3N4-NS的负载能力及释药行为。结果显示g-C3N4-NS呈片状结构,在离子环境中易层层自组装导致絮凝沉降,PEI修饰可实现g-C3N4-NS表面电荷切换并明显改善其稳定性。细胞毒性实验和斑马鱼胚胎发育毒性实验结果表明PEI-g-C3N4-NS质量浓度低于800μg·mL-1时毒性较低。作为药物载体,PEI-g-C3N4-NS巨大的比表面积及表面电荷作用使其对Sal B的最大负载率可达到327.4%并能持续缓慢释放药物,7天累积释放率达79.2%,体外释放过程符合Higuchi方程。综上,本研究制备的PEI修饰的g-C3N4-NS具有良好的生物相容性和高稳定性,在水溶性药物的高负载和缓释应用方面展现出良好的前景。Delivering water-soluble drugs via carriers often causes problems such as low loading and rapid releasing,so it is an urgent need to construct a high-load sustained-release drug delivery system for the clinical application of water-soluble drugs.Two-dimensional layered nanomaterials exhibit great potential in drug delivery due to their high specific surface area.In this study,bulk graphitic carbon nitride(b-g-C3N4)was obtained by calcination of urea.Graphitic carbon nitride nanosheets(g-C3N4-NS)were made from an alkali chemical-ultrasonicassisted stripping process.Scanning electron microscopy,transmission electron microscopy and atomic force microscopy were adopted to observe the morphological characteristics of g-C3N4-NS,while the structural charac‐teristics of g-C3N4-NS were analyzed by X-ray diffractometer and Fourier transform infrared spectroscopy.Ultra‐violet spectrometry and fluorescence spectrometry were used to investigate the optical properties of g-C3N4-NS,and scanning electron microscopy and X-ray diffractometer were employed to investigate the stability of g-C3N4-NS Polyethyleneimine(PEI)was applied in the study to functionally modify g-C3N4-NS,and salvianolic acid B(Sal B)was used as a water-soluble drug model to investigate the loading capacity and drug releasing behavior of g-C3N4-NS The results showed that g-C3N4-NS had a sheet structure,and it is easy to self-assemble in layers in the ionic environment to create flocculating settling.PEI modification can lead to the switching in the surface charge of g-C3N4-NS and significantly improve its stability.The results of cytotoxicity test and zebrafish embryo toxicity test showed that the toxicity was low when the concentration of PEI-g-C3N4-NS was less than 800μg·mL-1.The large specific surface area and surface charge of PEI-g-C3N4-NS allow the maximum load factor over Sal B to reach327.4%.In addition,PEI-g-C3N4-NS can continuously release drugs slowly,with a cumulative release rate of79.2%in seven straight days.The release process conforms to t

关 键 词：石墨相氮化碳 丹酚酸B 二维层状材料 水溶性药物 缓释 

分 类 号：R943[医药卫生—药剂学]