载姜黄素两亲性星状聚酯纳米粒的制备、表征及体外抗肿瘤研究  

Preparation,characterization and in vitro anti-tumor evaluation of curcuminloaded star-shaped polyester nanoparticles

作　　者：洪伟勇[1,2] 王金明[1] 王海英[1] 周雪峰 郭钫元[2] 杨根生[2] HONG Wei-yong;WANG Jin-ming;WANG Hai-ying;ZHOU Xue-feng;GUO Fang-yuan;YANG Gen-sheng(Department of Pharmcy,Taizhou Municipal Hospital,Taizhou 318000,China;College of Pharmaceutical Sciences,Zhejiang University of Technology,Hangzhou 310032,China)

机构地区：[1]台州市立医院药剂科,浙江台州318000 [2]浙江工业大学药学院,浙江杭州310032

出　　处：《中草药》2021年第8期2237-2246,共10页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金项目(22078297);浙江省自然科学基金项目(LY19B060012);浙江省药学会医院药学专项科研基金项目(2017ZYY28);浙江省药学会医院药学专项科研基金项目(2016ZYY35);台州市科技计划项目(1901ky49)。

摘　　要：目的制备载姜黄素两亲性星状聚酯纳米粒(Cur-NPs),以解决其稳定性差、生物利用度低等问题。方法通过开环聚合反应和酯化反应合成两亲性星状聚酯(DPE-PCL-m PEG)作为纳米粒的载体材料,傅立叶变换显微红外光谱(FT-IR)、1H-NMR和凝胶渗透色谱(GPC)表征确定其结构和相对分子质量。溶剂挥发法制备Cur-NPs,考察其粒径、ξ电位、载药量、包封率。对Cur-NPs进行稳定性、体外释放、材料安全性、体外抗肿瘤和细胞摄取能力考察。结果成功合成DPE-PCLm PEG,制备的Cur-NPs平均粒径为(86.00±2.01)nm,ξ电位为(-9.40±0.09)m V,包封率为(95.51±1.23)%,载药量为(5.52±0.54)%。Cur-NPs具有良好的稳定性和缓释能力。细胞毒性、细胞摄取和体外抗肿瘤实验表明,空白纳米粒(blankNPs)具有良好的生物安全性;相对于姜黄素溶液,Cur-NPs对人胶质瘤U251细胞的生长抑制作用更明显,并且具有更强的入胞能力。结论Cur-NPs理化性质理想,能有效提高药物体外生物活性,为姜黄素的临床应用提供了新的解决方案。Objective Curcumin loaded amphiphilic star-shaped polyester nanoparticles(Cur-NPs)were prepared to improve the bioavailability of curcumin.Methods Amphiphilic star-shaped polymers(DPE-PCL-m PEG)were synthesized by ring-opening polymerization and esterification and used as the polymer precursor of nanoscale drug carrier.The structures of polymers were characterized by FT-IR spectroscopy and 1H-NMR.The molecular weights of polymers were determined via GPC.Cur-NPs were prepared by solvent evaporation.The physicochemical properties such as particle size,zeta potential,drug loading,encapsulation efficiency,stability,in vitro drug release behavior and cytotoxicity,anti-proliferation efficacy and cellular uptake of Cur-NPs were studied.Results DPE-PCL-m PEG was successfully synthesized.The particle size,ξpotential,encapsulation efficiency and drug loading of Cur-NPs was(86.00±2.01)nm,ξpotential(-9.40±0.09)mV,(95.51±1.23)%and(5.52±0.54)%,respectively.In addition,the nanoparticles exhibited good stability and sustained release ability.In vitro cytotoxicity demonstrated that blank nanoparticles(blank-NPs)had favorable biosafety.Cur-NPs exhibited stronger anti-proliferation efficacy and better cellular uptake ability against U251 cell.Conclusion Cur-NPs with ideal physicochemical properties were successfully prepared.This novel nanocarrier system can effectively improve the bioavailability of curcumin and have potential applications in drug delivery.

关 键 词：两亲性星状聚酯 纳米粒 姜黄素 体外释放 人胶质瘤U251细胞 抗肿瘤 稳定性 开环聚合反应 生物利用度 酯化反应 溶剂挥发法 缓释 细胞毒性 细胞摄取 生物安全性 

分 类 号：R283.6[医药卫生—中药学]