葛根多糖载葛根素纳米粒温敏凝胶的制备及其药动学研究  

Preparation of Pueraria polysaccharides-loaded puerarin nanoparticles thermosensitive gel and its pharmacokinetics

作　　者：甘慧琴 梅陈松 关志宇[1] 谢树英 张紫霞 刘子鸣 吴文婷 朱卫丰[1] GAN Huiqin;MEI Chensong;GUAN Zhiyu;XIE Shuying;ZHANG Zixia;LIU Ziming;WU Wenting;ZHUWeifeng(Jiangxi University of Chinese Medicine,Nanchang 330004,China)

机构地区：[1]江西中医药大学,江西南昌330004

出　　处：《中草药》2024年第21期7238-7247,共10页Chinese Traditional and Herbal Drugs

基　　金：国家重点研发计划中医药现代化研究重点专项(2018ZX09721002);江西省人事厅博士后科研项目(252591);江西省教育厅科学技术研究项目(GJJ211239);江西中医药大学中药学一流学科科研项目(JXSYLXK-ZHYAO049);江西省中医药管理局科技计划项目(2020B0366)。

摘　　要：目的 制备含葛根多糖载葛根素纳米粒的温敏凝胶(Pueraria polysaccharides-loaded puerarin nanoparticles thermosensitive gel,PN/Pur-NPs-Gel),以提高其生物利用度。方法 对葛根多糖进行氨基化修饰合成氨基化葛根多糖(Pueraria polysaccharides-NH_(2),PN),并验证其结构;以PN为载体通过溶剂挥发法制备载葛根素纳米粒(PN/Pur-NPs),采用泊洛沙姆407和泊洛沙姆188为凝胶基质,制备PN/Pur-NPs-Gel,对PN/Pur-NPs-Gel的pH值、胶凝温度、流变学性质和体外释放进行考察;选用雄性大鼠对PN/Pur-NPs和PN/Pur-NPs-Gel进行药动学研究。结果 通过傅里叶变换红外光谱(Fourier transform infrared spectrometer,FTIR)和核磁共振氢谱(1H nuclear magnetic resonance spectra,1H-NMR)确认PN合成成功;制备的PN/Pur-NPs平均粒径为(140.47±0.75)nm、多分散指数(polydispersity index,PDI)为0.202±0.011,ζ电位为(-12.37±0.81)m V,包封率和载药量分别为(24.34±0.67)%、(15.63±0.23)%,且冻干后无明显变化,FTIR研究证实其无新化合物形成;PN/Pur-NPs-Gel的pH值为6.50±0.02、胶凝温度为(32.17±0.32)℃,流变学特性考察结果表明,PN/Pur-NPs-Gel的相变温度为26℃、在鼻腔环境中能够迅速形成凝胶,体外释放研究结果证实,PN/Pur-NPs-Gel可以有效结合纳米粒和凝胶的优势,具有较好的缓释作用;药动学研究结果表明,较葛根素原料药组,PN/Pur-NPs和PN/Pur-NPsGel的相对生物利用度分别提高到184.64%、219.53%,且MRT_(0~t)分别是葛根素原料药组的1.47、1.80倍。结论 将纳米技术和凝胶相结合后,制备的PN/Pur-NPs-Gel可以提高葛根素的生物利用度,并延长PN/Pur-NPs在鼻腔停留时间,为开发新的葛根素制剂提供实验基础。Objective To prepare Pueraria polysaccharides-loaded puerarin nanoparticles thermosensitive gel(PN/Pur-NPs-Gel)in order to improve its bioavailability.Methods Amino modified Pueraria polysaccharides were synthesised as Pueraria polysaccharides-NH_(2)(PN)and their structures were verified;Puerarin-loaded nanoparticles(PN/Pur-NPs)were prepared by solvent volatilisation using PN as a carrier,and PN/Pur-NPs-Gel was prepared by using Porloxacin 407 and Porloxacin 188 as gel matrix,and the pH values,gelling temperature,rheological properties,and in vitro release were investigated;male rats were selected for pharmacokinetic studies of PN/Pur-NPs and PN/Pur-NPs-Gel.Results The successful synthesis of PN was confirmed by Fourier transform infrared spectrometer(FTIR)and 1H nuclear magnetic resonance spectra(1H-NMR);the prepared PN/Pur-NPs had a particle size of(140.47±0.75)nm,a polydispersity index(PDI)of 0.202±0.011,and aζpotential of(−12.37±0.81)mV,with encapsulation efficiency and drug loading of(24.34±0.67)%and(15.63±0.23)%,respectively,and no significant changes after lyophilisation.Infrared spectroscopy study confirmed that no new compounds were formed;the pH of PN/Pur-NPs-Gel was 6.50±0.02,and the gelation temperature was(32.17±0.32)℃.The results of the rheological investigation showed that the phase transition temperature of PN/Pur-NPs-Gel was 26℃,and the gel could be formed rapidly in the nasal environment.The results of in vitro release confirmed that PN/Pur-NPs-Gel could effectively combine the advantages of nanoparticles and gels,and had a better sustained-release effect;the results of pharmacokinetic study showed that compared with the puerarin group,the relative bioavailability of PN/Pur-NPs and PN/Pur-NPs-Gel was increased to 184.64%and 219.53%,respectively,and the MRT_(0-t) was 1.47 and 1.80 times higher than that of puerarin group,respectively.Conclusion The prepared PN/Pur-NPs-Gel after combining nanotechnology and gel can improve the bioavailability of puerarin and prolong the residence tim

关 键 词：葛根素 葛根多糖 鼻腔给药 纳米粒 温敏凝胶 药动学 生物利用度 缓释作用 

分 类 号：R283.6[医药卫生—中药学]