Abo El-Enin Hadel A, Elkomy Mohammed H, Naguib Ibrahim A, Ahmed Marwa F, Alsaidan Omar A, Alsalahat Izzeddin, Ghoneim Mohammed M, Eid Hussein M
Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
Department of Pharmaceutics, College of Pharmacy, Jouf University, P.O. Box 2014, Sakaka 72341, Saudi Arabia.
Pharmaceuticals (Basel). 2022 Feb 24;15(3):281. doi: 10.3390/ph15030281.
This research aimed to design, optimize, and evaluate berberine-laden nanostructured lipid carriers overlaid with chitosan (BER-CTS-NLCs) for efficient brain delivery via the intranasal route. The nanostructured lipid carriers containing berberine (BER-NLCs) were formulated via hot homogenization and ultrasonication strategy and optimized for the influence of a variety of causal variables, including the amount of glycerol monostearate (solid lipid), poloxamer 407 (surfactant) concentration, and oleic acid (liquid lipid) amount, on size of the particles, entrapment, and the total drug release after 24 h. The optimal BER-NLCs formulation was then coated with chitosan. Their diameter, in vitro release, surface charge, morphology, ex vivo permeability, pH, histological, and in vivo (pharmacokinetics and brain uptake) parameters were estimated. BER-CTS-NLCs had a size of 180.9 ± 4.3 nm, sustained-release properties, positive surface charge of 36.8 mV, and augmented ex-vivo permeation via nasal mucosa. The histopathological assessment revealed that the BER-CTS-NLCs system is safe for nasal delivery. Pharmacokinetic and brain accumulation experiments showed that animals treated intranasally with BER-CTS-NLCs had substantially greater drug levels in the brain. The ratios of BER brain/blood levels at 30 min, AUC/AUC, drug transport percentage, and drug targeting efficiency for BER-CTS-NLCs (IN) were higher compared to BER solution (IN), suggesting enhanced brain targeting. The optimized nanoparticulate system is speculated to be a successful approach for boosting the effect of BER in treating CNS diseases, such as Alzheimer's disease, through intranasal therapy.
本研究旨在设计、优化并评估负载黄连素的壳聚糖包被纳米结构脂质载体（BER-CTS-NLCs），以通过鼻内途径实现高效脑递送。含黄连素的纳米结构脂质载体（BER-NLCs）通过热均质化和超声处理策略制备，并针对多种影响因素进行优化，包括单硬脂酸甘油酯（固体脂质）用量、泊洛沙姆407（表面活性剂）浓度以及油酸（液体脂质）用量对颗粒大小、包封率和24小时后药物总释放量的影响。然后用壳聚糖包被优化后的BER-NLCs制剂。评估了它们的直径、体外释放、表面电荷、形态、离体渗透率、pH值、组织学以及体内（药代动力学和脑摄取）参数。BER-CTS-NLCs的粒径为180.9±4.3 nm，具有缓释特性，表面正电荷为36.8 mV，并且经鼻黏膜的离体渗透增强。组织病理学评估显示，BER-CTS-NLCs系统用于鼻腔给药是安全的。药代动力学和脑蓄积实验表明，经鼻给予BER-CTS-NLCs的动物脑内药物水平显著更高。与BER溶液（鼻内给药）相比，BER-CTS-NLCs（鼻内给药）在30分钟时的脑/血药浓度比、AUC/AUC、药物转运百分比和药物靶向效率更高，表明脑靶向性增强。推测优化后的纳米颗粒系统是一种通过鼻内治疗增强黄连素治疗中枢神经系统疾病（如阿尔茨海默病）效果的成功方法。
