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Olanzapine Mesoporous Nanostructured Lipid Carrier: Optimization, Characterization, In Vivo Assessment, and Physiologically Based Pharmacokinetic Modeling
IEEE Transactions on NanoBioscience ( IF 3.9 ) Pub Date : 2021-01-25 , DOI: 10.1109/tnb.2021.3052080
Hussein O. Ammar , Mahmoud M. Ghorab , Marwa S. Saleh , Amira M. Ghoneim

A promising approach has been emerging to enhance dissolution of hydrophobicdrugsby encapsulation in mesoporous silica materials. Olanzapine is a practically insoluble antipsychotic drug which is subjected to excessive first pass effect and shows inadequate oral bioavailability. Therefore, mesoporous silica was used to improve bioavailability of olanzapine incorporated in nano-structured lipid carriers (NLCs). These systems were characterized for their particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE) and differential scanning calorimetry (DSC) as well asits release profile. The optimized mesoporous NLC system displayed nano-spherical particles (120.56 nm), possessed high entrapment efficiency (88.46%) and the highest percentage of drug released after six hours (75.13%). The biological performance of the optimized system was assessed in comparison with the drug suspension in healthy albino rabbits. The optimized system showed significantly (P < 0.05) prolonged MRT (8.47 h), higher C max (22.12± 0.40 ng/ml) and T max (2.0 h) values compared to drug suspension. Physiologically based pharmacokinetic (PBPK) model was simulated and verified. All the predicted results were within 0.6 and 1-fold of the reported data. To set a conclusion, in vitro results as well as in vivo pharmacokinetic study and PBPK data showed an enhancement in bioavailability of the optimized NLCs system over the plain drug suspension. These results proved the potentiality of incorporating olanzapine in mesoporous NLC for a significant improvement in oral bioavailability of olanzapine.

中文翻译:

奥氮平介孔纳米结构脂质载体:优化、表征、体内评估和基于生理的药代动力学建模

通过封装在介孔二氧化硅材料中来增强疏水性药物的溶解度的有前景的方法已经出现。奥氮平是一种几乎不溶的抗精神病药,具有过度的首过效应,口服生物利用度不足。因此,介孔二氧化硅被用于提高纳米结构脂质载体(NLCs)中奥氮平的生物利用度。这些系统的特征在于它们的粒径、多分散指数 (PDI)、zeta 电位、包封率 (EE) 和差示扫描量热法 (DSC) 及其释放曲线。优化的介孔 NLC 系统显示出纳米球形颗粒(120.56 nm),具有高包封率(88.46%)和最高的六小时后药物释放百分比(75.13%)。与健康白化兔中的药物混悬液相比,对优化系统的生物学性能进行了评估。优化后的系统显示出显着(P < 0.05)延长的 MRT(8.47 h),更高的 C 与药物悬浮液相比的最大值(22.12± 0.40 ng/ml) 和 T max (2.0 h) 值。模拟并验证了基于生理学的药代动力学 (PBPK) 模型。所有预测结果均在报告数据的 0.6 和 1 倍以内。为了得出结论,体外 结果以及 体内药代动力学研究和 PBPK 数据显示优化的 NLCs 系统的生物利用度比普通药物悬浮液有所提高。这些结果证明了在介孔 NLC 中加入奥氮平显着提高奥氮平口服生物利用度的潜力。
更新日期:2021-04-02
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