目的 制備甘草酸（GL）-普朗尼克F127（F127）/聚乙二醇1000維生素E琥珀酸酯（TPGS）混合納米膠束（MMs）（GL-F127/TPGS-MMs），以改善GL的口服吸收。方法 采用薄膜分散法制備GL-F127/TPGS-MMs，以膠束包封率、載藥量為評價(jià)指標(biāo)，單因素實(shí)驗(yàn)優(yōu)化處方及工藝，包括F127與TPGS的比例、聚合物的質(zhì)量濃度、GL的用量、水化溫度、水化時(shí)間；采用透射電鏡考察膠束形態(tài)；以吸收速率常數(shù)（K_a）和表觀吸收系數(shù)（P_app）為評價(jià)指標(biāo)，采用大鼠在體單向腸灌流法考察GL-F127/TPGS-MMs的腸吸收特性。結(jié)果 優(yōu)化得到處方和工藝為TPGS 180 mg、F127 270 mg、GL 70 mg、水化溫度50 ℃、水化時(shí)間3 h。所制備GL-F127/TPGS-MMs澄明度好，平均粒徑為（28.20±5.63）nm，多分散系數(shù)為0.20±0.06，Zeta電位為（-5.24±1.55）mV，包封率為（97.57±5.29）%，載藥量為（13.13±0.71）%；膠束呈球形，可見明顯的囊泡結(jié)構(gòu)。與回腸段比較，GL在空腸段吸收較好，且差異有統(tǒng)計(jì)學(xué)意義（P<0.05）；與GL原料藥比較，GL-F127/TPGS-MMs的腸吸收較好，且差異有統(tǒng)計(jì)學(xué)意義（P<0.05）。結(jié)論 所制備的GL-F127/TPGS-MMs顯著地提高了GL的體內(nèi)吸收。

Objective To prepare glycyrrhizic acid (GL)-Pluronic F127 (F127)/polyethylene glycol 1000 vitamin E succinate (TPGS) mixed nanomicelles (MMs) and improve oral absorption of GL. Methods GL-F127/TPGS-MMs was prepared by thin film dispersion method. The encapsulation efficiency and drug loading of MMs were used as evaluation indexes. The formulation and process, including the ratio of F127 to TPGS, the concentration of polymer and GL, hydration temperature and time, were optimized by the single factor experiment. The morphology of MMs was investigated by transmission electron microscopy. The single-pass perfusion model was established in rats to investigate the intestinal absorption characteristics of GL-F127/TPGS-MMs with absorption rate constant (K_a) and apparent absorption coefficient (P_app) as evaluation indexes. Results The optimal formulation and process of GL-F127/TPGS-MMs were as follows:TPGS 180 mg, F127 270 mg, GL 70 mg, hydration temperature 50℃ and hydration time 3 h. The prepared GL-F127/TPGS-MMs had good clarity and the particle size, polydispersity index, and Zeta potential were (28.20±5.63) nm, 0.20±0.06, and (-5.24±1.55) mV, respectively. The encapsulation efficiency and drug loading were (97.57±5.29)% and (13.13±0.71)%, respectively. The MMs were spherical with distinct vesicle structure. The absorption of GL in the jejunum segment was significantly higher than that in the ileum segment (P<0.05). Compared with raw GL, GL-F127/TPGS-MMs had a statistically significant higher absorption rate in the intestinal segment (P<0.05). Conclusion The prepared GL-F127/TPGS-MMs could significantly improve the absorption of GL in vivo.

R283.6

國家自然科學(xué)基金項(xiàng)目（81803741）；北京市科委重點(diǎn)項(xiàng)目（Z171100001717026）