用于增强阿糖胞苷肠道吸收及体内治疗急性髓系白血病疗效的双分子层脂质体和非离子表面活性剂泡囊
Bilosomes and Niosomes for Enhanced Intestinal Absorption and In Vivo Efficacy of Cytarabine in Treatment of Acute Myeloid Leukemia.
作者信息
Said Abdelrahman R, Arafa Mona F, El-Dakroury Walaa A, Alshehri Sultan, El Maghraby Gamal M
机构信息
Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City 11829, Egypt.
出版信息
Pharmaceuticals (Basel). 2024 Nov 23;17(12):1572. doi: 10.3390/ph17121572.
UNLABELLED
Cytarabine (CTR) is a hydrophilic anticancer drug used to treat leukemia. It suffers from poor permeability and intestinal metabolism, diminishing its oral bioavailability.
BACKGROUND/OBJECTIVES: The objective was to develop and evaluate niosomes and bilosomes for enhanced intestinal absorption; hence, oral bioavailability.
RESULTS
CTR-loaded niosomes and bilosomes with vesicle sizes of 152 and 204.3 nm were successfully prepared with acceptable properties. The presence of bile salts increased the zeta potential of bilosomes. The recorded entrapment efficiency of cytarabine was acceptable for such a hydrophilic drug. CTR-bilosomes showed a pH-dependent drug release pattern with preferred release in pH 6.8. Intestinal absorption behavior indicated a site-dependent CTR absorption pattern with unfavorable absorption in the distal intestine. Niosomal and bilosomal formulations enhanced intestinal absorption parameters with evidence for a predominant paracellular absorption mechanism that bypasses intestinal barriers. The investigation of the anti-leukemic effect of niosomal and bilosomal formulations indicated that both formulations ameliorated the blood parameters, reflecting significant improvement in leukemia treatment compared with the drug solution. Pathological examination of blood films revealed decreased blast cells in peripheral blood in groups treated with tested formulations.
METHODS
Tested formulations were prepared according to the pro-concentrate method and characterized for particle size, zeta potential, entrapment efficiency, and in vitro release. CTR-loaded niosomes and bilosomes were evaluated for enhanced intestinal absorption utilizing the single-pass in situ intestinal perfusion method in rabbits, and the anti-leukemic effect was assessed using the benzene-induced leukemia model in rats.
CONCLUSIONS
This study introduced surfactant vesicles for enhanced oral bioavailability of CTR.
未标记
阿糖胞苷（CTR）是一种用于治疗白血病的亲水性抗癌药物。它存在通透性差和肠道代谢问题，降低了其口服生物利用度。
背景/目的：目的是开发和评估用于增强肠道吸收的非离子型脂质体和双分子层脂质体，从而提高口服生物利用度。
结果
成功制备了囊泡大小分别为152和204.3 nm的载CTR非离子型脂质体和双分子层脂质体，其性质良好。胆盐的存在增加了双分子层脂质体的ζ电位。对于这种亲水性药物，所记录的阿糖胞苷包封率是可以接受的。CTR双分子层脂质体表现出pH依赖性药物释放模式，在pH 6.8时优先释放。肠道吸收行为表明CTR的吸收具有部位依赖性，在远端肠道吸收不佳。非离子型脂质体和双分子层脂质体制剂增强了肠道吸收参数，有证据表明主要通过细胞旁路吸收机制绕过肠道屏障。对非离子型脂质体和双分子层脂质体制剂的抗白血病作用研究表明，两种制剂均改善了血液参数，与药物溶液相比，白血病治疗有显著改善。血涂片的病理检查显示，用受试制剂治疗的组外周血中的原始细胞减少。
方法
受试制剂根据预浓缩法制备，并对粒径、ζ电位、包封率和体外释放进行表征。利用家兔单通道原位肠道灌注法评估载CTR非离子型脂质体和双分子层脂质体的肠道吸收增强情况，并使用大鼠苯诱导的白血病模型评估其抗白血病作用。
结论
本研究引入了表面活性剂囊泡以提高CTR的口服生物利用度。
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