Department of Clinical Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
J Liposome Res. 2020 Jun;30(2):150-162. doi: 10.1080/08982104.2019.1610434. Epub 2019 May 16.
The present study aimed to formulate and evaluate metformin sterosomes. Sterosomes were prepared by incorporating stearylamine and cholesterol in different ratios. Sterosomes were characterized using size, zeta potential, entrapment efficiency (EE%) and release. Aerosol generated by nebulization was evaluated by a cooled Andersen cascade impactor (ACI) at 15 L/min. cytotoxicity of free and metformin-containing sterosomes was tested against human cancer cell lines. A comparative pharmacokinetic study between sterosomal formulation and free drug solution (750 mg) was performed. Spirometry was performed before and at time intervals after inhalation. The mean hydrodynamic diameter of the formulated vesicles was in the range of 288.7-578 nm. The EE% varied from 71 ± 1.4% to 89 ± 5.2%, with an optimum EE% of 89 ± 5.2at a lipid ratio of 2/1 stearylamine/cholesterol. Metformin sterosomes displayed an inhibitory effect on A549 lung cancer cell lines which significantly ( < 0.05) increased depending on dose and prolonged exposure time. Spirometric data were minimally changed before and after inhalation without a statistically significant difference in the forced expiratory volume in one second (FEV), forced vital capacity (FVC) or FEV/FVC ratio ( > 0.05). Metformin-loaded sterosomes resulted in a significant increase in biological half-life () with a mean value of 7.31 ± 1.04 h compared to 3.99 ± 0.17 h of the solution form. However, the peak plasma concentration of metformin sterosomes was lower than that achieved by metformin-free solution aerosol, and the difference was statistically significant ( < 0.05).The eligibility of sterosomes for aerosol delivery by nebulization would provide a novel strategy for delivery of metformin by inhalation as a potentially effective inhalation treatment of lung cancer.
本研究旨在制备和评价二甲双胍甾醇体。甾醇体是通过以不同比例掺入硬脂胺和胆固醇制备的。采用粒径、Zeta 电位、包封率（EE%）和释放度对甾醇体进行表征。通过 15 L/min 的冷却 Andersen 级联撞击器（ACI）评估雾化产生的气溶胶。对游离和含有二甲双胍的甾醇体进行了人癌细胞系的细胞毒性测试。对甾醇体制剂与游离药物溶液（750mg）进行了比较药代动力学研究。在吸入前后进行了肺活量测定。所制备的囊泡的平均水动力学直径在 288.7-578nm 范围内。EE% 从 71±1.4%变化到 89±5.2%，在硬脂胺/胆固醇的脂质比为 2/1 时，EE%达到最佳值 89±5.2%。二甲双胍甾醇体对 A549 肺癌细胞系有抑制作用，且抑制作用随着剂量和延长暴露时间的增加而显著增加（<0.05）。吸入前后的肺活量数据变化极小，且一秒用力呼气量（FEV）、用力肺活量（FVC）或 FEV/FVC 比值无统计学差异（>0.05）。与溶液形式的 3.99±0.17h 相比，载有二甲双胍的甾醇体使生物半衰期（）显著增加，平均为 7.31±1.04h。然而，二甲双胍甾醇体的血浆峰浓度低于游离二甲双胍溶液气雾剂的浓度，且差异具有统计学意义（<0.05）。甾醇体通过雾化给药的适宜性为通过吸入给药提供了一种新型的二甲双胍输送策略，可能是治疗肺癌的有效吸入治疗方法。
