聚酰胺-胺树枝状大分子包载白藜芦醇的制备及体外研究  

Preparation and in vitro study of polyamide-amine dendrimer-loaded resveratrol

作　　者：常子晨 李颖 张颖 阴龙飞 刘春艳 CHANG Zi-chen;LI Ying;ZHANG Ying;YIN Long-fei;LIU Chun-yan(College of Pharmacy,North China University of Science and Technology,Tangshan 063200,China;Department of Pharmacy,General Hospital of Coal Group,Tonghua Hospital Management Company,Datong 037005,China)

机构地区：[1]华北理工大学药学院,河北唐山063200 [2]同华医院管理公司同煤集团总医院药学部,山西大同037005

出　　处：《中草药》2019年第24期5963-5969,共7页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(21302040)

摘　　要：目的 制备聚酰胺-胺树枝状大分子包载白藜芦醇纳米载体复合物(Res-PAMAM-Ac),并考察其稳定性和安全性。方法 采用发散法合成空白载体,并进行乙酰化修饰,核磁共振图谱(1H-NMR)、红外光谱(IR)对载体进行表征,粒径及Zeta电位检测考察载体性质;逆相蒸发法制备Res-PAMAM-Ac,HPLC检测载药量、包封率以及稳定性;MTT法考察载体和复合物对人肺癌A549细胞的细胞毒性;溶血性试验评价载体和复合物的生物安全性。结果 成功合成Res-PAMAM-Ac,大小均匀,平均粒径(167.30±21.70)nm,PDI为0.115±0.006,电位(19.27±0.35)m V;平均载药量(76.99±1.30)mg/g,包封率(29.63±2.70)%,稳定性参数(KE)小于0.15,且药物无明显析出;复合物质量浓度在30μg/m L以下时对人肺癌A549细胞具有较小毒性;载体及复合物溶血率低于5%,视为生物安全。结论 制备的Res-PAMAM-Ac粒径均匀、载药量较好、稳定性高、毒性小。Objective The resveratrol nanocarrier complex(Res-PAMAM-Ac)was encapsulated by polyamide-amine dendrimer,its stability and safety was investigated.Methods The blank carriers were synthesized by the divergence method and acetylated.Characterization of the nanocarriers was investigated by'H-NMR and IR.The properties of carriers were investigated by particle size and zeta potential.Res-PAMAM-Ac was prepared by reverse-phase evaporation method,and the drug loading,encapsulation rate and stability were examined by HPLC.The cytotoxicity of nanocarriers and complex on human lung cancer A549 cells were investigated by MTT method.The biosafety of nanocarriers and complex was inspected by hemolysis test.Results Res-PAMAM-Ac nanocarrier complex was synthesized successfully.The particle size of Res-PAMAM-Ac was(167.30±21.70)nm,PDI was 0.115±0.006 and the zeta potential was(19.27±0.35)mV.The average drug loading of Res-PAMAM-Ac was(76.99±1.30)mg/g and the encapsulation rate was(29.63±2.7)%.The stability parameter(Ke)was less than 0.15,no obvious drug precipitation was observed.Cytotoxicity tests showed that Res-PAMAM-Ac was less toxic to human lung cancer A549 cells when the concentration was below 30 fig/mL.The hemolysis rate of the nanocarriers and complex was less than 5%,which can be considered as biosafety.Conclusion Res-PAMAM-Ac nanocarrier complex with uniform particle size,high stability,good drug loading and low toxicity was prepared.

关 键 词：白藜芦醇纳米载体复合物 聚酰胺-胺树枝状大分子 载药量 稳定性 细胞毒性 安全性 发散法 逆相蒸发法 HPLC 包封率 MTT法 人肺癌A549细胞 溶血性试验 

分 类 号：R283.6[医药卫生—中药学]