醋酸阿比特龙脂质纳米乳的制备、评价与生物利用度研究

Preparation,evaluation and bioavailability study of abiraterone acetate-loaded lipid nanoemulsion

摘要

目的: 提高醋酸阿比特龙 (abiraterone acetate,ABA) 的口服生物利用度,减少给药剂量,消除其严重的食物效应。方法: 采用高压均质法制备醋酸阿比特龙脂质纳米乳 (ABA-loaded lipid nanoemulsion, ABA-NE),通过单因素实验与正交设计优化处方与工艺参数,并对制剂的粒径、多分散指数 (polydispersity index,PDI) 、Zeta 电位及包封率进行表征。以比格犬为模型动物,进行体内药动学研究,比较 ABA-NE 与原研片剂的生物利用度。结果: 优化所得 ABA-NE 呈白色均一乳状,平均粒径为 (195.61±3.12) nm,PDI 为 (0.05±0.01),Zeta 电位为-(48.17±2.64) mV,包封率达 (95.76±1.59) %,载药量为 (39.84±0.23) mg⋅mL^-1。药动学结果表明,与醋酸阿比特龙原研片剂相比,ABA-NE 的C_max 和 AUC 显著提高,口服相对生物利用度为原研片剂的16.06倍。结论: ABA-NE 能显著提高 ABA 的口服生物利用度,有望降低临床给药剂量,同时为消除食物效应提供了潜在策略,未来需要进一步通过餐后实验验证。

Abstract

Objective: To improve the oral bioavailability of abiraterone acetate (ABA), reduce the administered dose, and eliminate its significant food effect. Methods: ABA-loaded lipid nanoemulsion (ABA-NE) was prepared by high-pressure homogenization.The formulation and process parameters were optimized through single-factor tests and orthogonal experimental design.The prepared ABA-NE was characterized for particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency.A pharmacokinetic study in beagle dogs was conducted to compare the bioavailability of ABA-NE with that of the reference tablets. Results: The optimized ABA-NE appeared as a white, homogeneous emulsion with average particle size of (195.61±3.12) nm, PDI of (0.05±0.01), Zeta potential of-(48.17±2.64) mV, encapsulation efficiency of (95.76±1.59) % and drug loading capacity of (39.84±0.23) mg⋅mL^-1.The pharmacokinetic study demonstrated that compared with the reference formulation, ABA-NE significantly increased the maximum plasma concentration (C_max) and the area under the concentration-time curve (AUC).The oral relative bioavailability of ABA-NE was 16.06-fold higher than that of the reference tablets. Conclusion: ABA-NE can significantly improve the oral bioavailability of ABA, which is expected to reduce the clinical dosage.It also provides a potential strategy for eliminating the effect of food. However, further experiments after meals are needed to verify this hypothesis.

关键词

醋酸阿比特龙 / 脂质纳米乳 / 高压均质 / 正交实验 / 药动学

Key words

abiraterone acetate / lipid nanoemulsion / high pressure homogenization / orthogonal test / pharmacokinetics

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