Zidan Ahmed S, Aldawsari Hibah
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia ; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
Drug Des Devel Ther. 2015 Jul 24;9:3885-98. doi: 10.2147/DDDT.S87906. eCollection 2015.
Delivering drugs to intracerebral regions can be accomplished by improving the capacity of transport through blood-brain barrier. Using sertraline as model drug for brain targeting, the current study aimed at modifying its liposomal vesicles with mannopyranoside. Box-Behnken design was employed to statistically optimize the ultrasound parameters, namely ultrasound amplitude, time, and temperature, for maximum mannosylation capacity, sertraline entrapment, and surface charge while minimizing vesicular size. Moreover, in vitro blood-brain barrier transport model was established to assess the transendothelial capacity of the optimized mannosylated vesicles. Results showed a dependence of vesicular size, mannosylation capacity, and sertraline entrapment on cavitation and bubble implosion events that were related to ultrasound power amplitude, temperature. However, short ultrasound duration was required to achieve >90% mannosylation with nanosized vesicles (<200 nm) of narrow size distribution. Optimized ultrasound parameters of 65°C, 27%, and 59 seconds for ultrasound temperature, amplitude, and time were elucidated to produce 81.1%, 46.6 nm, and 77.6% sertraline entrapment, vesicular size, and mannosylation capacity, respectively. Moreover, the transendothelial ability was significantly increased by 2.5-fold by mannosylation through binding with glucose transporters. Hence, mannosylated liposomes processed by ultrasound could be a promising approach for manufacturing and scale-up of brain-targeting liposomes.
通过提高药物穿过血脑屏障的转运能力，可以实现将药物递送至脑内区域。本研究以舍曲林作为脑靶向模型药物，旨在用甘露吡喃糖苷修饰其脂质体囊泡。采用Box-Behnken设计对超声参数（即超声振幅、时间和温度）进行统计学优化，以实现最大的甘露糖基化能力、舍曲林包封率和表面电荷，同时使囊泡尺寸最小化。此外，建立了体外血脑屏障转运模型，以评估优化后的甘露糖基化囊泡的跨内皮细胞转运能力。结果表明，囊泡大小、甘露糖基化能力和舍曲林包封率依赖于与超声功率振幅、温度相关的空化和气泡内爆事件。然而，需要较短的超声持续时间才能使尺寸分布窄的纳米级囊泡（<200 nm）实现>90%的甘露糖基化。阐明了超声温度、振幅和时间的优化超声参数分别为65°C、27%和59秒，可产生81.1%的舍曲林包封率、46.6 nm的囊泡大小和77.6%的甘露糖基化能力。此外，通过与葡萄糖转运体结合进行甘露糖基化可使跨内皮细胞能力显著提高2.5倍。因此，通过超声处理的甘露糖基化脂质体可能是一种用于制备和扩大规模的脑靶向脂质体的有前景的方法。
