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-NH₂，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）mV，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-NPs-Gel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-NH₂ (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 a ζ potential 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 time of PN/Pur-NPs in the nasal cavity, which provides an experimental basis for the development of new puerarin formulations.

R283.6

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)