Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts, 02115, USA.
Translational Modeling & Simulation, Quantitative Clinical Pharmacology, Takeda Pharmaceuticals, Cambridge, Massachusetts, 02139, USA.
Pharm Res. 2019 Jul 11;36(9):134. doi: 10.1007/s11095-019-2667-7.
Despite extensive preclinical investigations, in-vivo properties and formulation characteristics that improve CNS drug delivery following systemic dosing of nanoemulsions remain incompletely understood.
The CNS targeting potential of systemically administered nanoemulsions was evaluated by formulating rapamycin containing fish oil nanoemulsions, and testing the combined effect of formulation characteristics such as the circulation half-life and particle size distribution, on CNS delivery of rapamycin containing fish oil nanoemulsions in mice.
Results generated with rapamycin nanoemulsions suggested that circulation half-life and particle size distribution did not impact the brain targeting efficiency of rapamycin containing fish oil nanoemulsions. Further, in the absence of any improvement in the systemic exposures of rapamycin, nanoemulsions did not outperform their aqueous counterpart with respect to the extent of CNS drug delivery.
Our findings confirm that BBB penetration, which primarily depends on intrinsic drug-related properties, may not be significantly improved following encapsulation of drugs in nanoemulsions. Graphical Abstract The CNS targeting potential of systemically administered nanoemulsions was investigated by formulating various rapamycin containing fish oil nanoemulsions associated with different formulation characteristics such as the circulation half-life and particle size distribution. The targeting efficiency (TE) defined as the ratio of the brain exposures to the accompanying systemic exposures of rapamycin was estimated for each formulation following IV dosing in mice.
尽管进行了广泛的临床前研究，但对于经全身给药后纳米乳剂改善中枢神经系统（CNS）药物传递的体内特性和制剂特征仍了解不完全。
通过制备含有鱼油的雷帕霉素纳米乳剂，并测试制剂特性（如循环半衰期和粒径分布）对含有鱼油的雷帕霉素纳米乳剂在小鼠中 CNS 传递的综合影响，评估全身给予纳米乳剂的 CNS 靶向潜力。
雷帕霉素纳米乳剂的结果表明，循环半衰期和粒径分布并不影响含有鱼油的雷帕霉素纳米乳剂的脑靶向效率。此外，在不改善雷帕霉素全身暴露的情况下，纳米乳剂在 CNS 药物传递的程度方面并不优于其水性对应物。
我们的研究结果证实，血脑屏障（BBB）穿透性可能不会因药物包封在纳米乳剂中而得到显著改善，这主要取决于内在的药物相关特性。
通过制备与循环半衰期和粒径分布等不同制剂特征相关的各种含有鱼油的雷帕霉素纳米乳剂，研究了全身给予纳米乳剂的 CNS 靶向潜力。在小鼠 IV 给药后，估计了每种制剂的靶向效率（TE），定义为雷帕霉素脑暴露与伴随的全身暴露之比。
