目的 制备根皮素聚乙二醇-聚乳酸［methoxy poly (ethylene glycol)-poly (lactic acid)，mPEG-PLA］纳米胶束（phloretin mPEG-PLA nanomicelles，Phl@mPEG-PLA/NM）处方，考察其口服药动学行为。方法 薄膜分散-探头超声法制备Phl@mPEG-PLA/NM。采用包封率、载药量、沉降率为指标，单因素结合Box-Behnken设计-效应面法优化处方。透射电子显微镜（TEM）观察外貌形态，透析法考察体外释药行为。SD大鼠分别ig给予根皮素混悬液和Phl@mPEG-PLA/NM，HPLC法测定根皮素血药浓度，计算主要药动学参数。结果 Phl@mPEG-PLA/NM最佳处方为mPEG-PLA用量为105 mg、水化体积为9.5 mL、水化温度40℃。包封率、载药量、沉降率、粒径及ζ电位分别为（88.52±1.86）%、（8.84±0.32）%、（8.04±0.23）%、（85.07±6.12）nm和（−23.56±1.49）mV。纳米胶束外貌为球形。Phl@mPEG-PLA/NM的半衰期（t_1/2）增加至（4.60±0.84）h，血药浓度（C_max）增加至（1 284.56±307.65）ng/mL，口服相对生物利用度提高至3.34倍。结论 Phl@mPEG-PLA/NM显著促进了根皮素口服吸收。

Objective To optimize the formulation of phloretin mPEG-PLA nanomicelles (Phl@mPEG-PLA/NM). Oral pharmacokinetic behavior in vivo was also studied. Methods Phl@mPEG-PLA/NM were prepared by thin film dispersion-probe ultrasonic method. Single factor experiments combined with Box-Behnken response surface design method was used to gain optimal prescriptions. Transmission electron microscope (TEM) was employed to observe its appearance. Release behavior of nanomicelles in vitro was investigated by dialysis method. SD rats in each group were administered intragastrically with phloretin suspension and Phl@mPEG-PLA/NM, respectively. Concentration of phloretin in plasma was analyzed by HPLC and the main pharmacokinetic parameters were calculated. Results Optimal formulation of Phl@mPEG-PLA/NM: mPEG-PLA amounts were 105 mg, hydration volume was 9.5 mL and hydration temperature was 40 ℃. Envelopment efficiency, drug loading, settlement rate, particle size and Zeta potential were (88.52 ±1.86)%, (8.84 ±0.32)%, (8.04 ±0.23)%, (85.07 ±6.12) nm and (−23.56 ±1.49) mV, respectively. The prepared nanomicelles were spherical. t_1/2 of Phl@mPEG-PLA/NM was increased to (4.60 ±0.84) h, C_max was enhanced to (1 284.56 ±307.65) ng/mL and oral relative bioavailability was increased to 3.34-fold. Conclusion Phl@mPEG-PLA/NM promoted oral absorption of phloretin effectively.

R283.6

河南省二〇二一年科技发展计划（212102310315）；上海市科委项目（21S21903400）