Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia.
Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia.
Int J Nanomedicine. 2018 Apr 27;13:2571-2584. doi: 10.2147/IJN.S151788. eCollection 2018.
Drugs that are effective against diseases in the central nervous system and reach the brain via blood must pass through the blood-brain barrier (BBB), a unique interface that protects against potential harmful molecules. This presents a major challenge in neuro-drug delivery. This study attempts to fabricate the cefuroxime-loaded nanoemulsion (CLN) to increase drug penetration into the brain when parenterally administered.
The nanoemulsions were formulated using a high-pressure homogenization technique and were characterized for their physicochemical properties.
The characterizations revealed a particle size of 100.32±0.75 nm, polydispersity index of 0.18±0.01, zeta potential of -46.9±1.39 mV, viscosity of 1.24±0.34 cps, and osmolality of 285.33±0.58 mOsm/kg, indicating that the nanoemulsion has compatibility for parenteral application. CLN was physicochemically stable within 6 months of storage at 4°C, and the transmission electron microscopy revealed that the CLN droplets were almost spherical in shape. The in vitro release of CLN profile followed a sustained release pattern. The pharmacokinetic profile of CLN showed a significantly higher , area under the curve (AUC) , prolonged half-life, and lower total plasma clearance, indicating that the systemic concentration of cefuroxime was higher in CLN-treated rats as compared to cefuroxime-free treated rats. A similar profile was obtained for the biodistribution of cefuroxime in the brain, in which CLN showed a significantly higher , AUC , prolonged half-life, and lower clearance as compared to free cefuroxime solution.
Overall, CLN showed excellent physicochemical properties, fulfilled the requirements for parenteral administration, and presented improved in vivo pharmacokinetic profile, which reflected its practical approach to enhance cefuroxime delivery to the brain.
作用于中枢神经系统且能通过血液到达大脑的药物必须穿过血脑屏障（BBB），这是一种独特的界面，可防止潜在的有害分子进入。这在神经药物输送方面带来了重大挑战。本研究试图制备头孢呋辛载纳米乳（CLN），以增加经肠胃外给药时药物向大脑的渗透。
采用高压匀质技术制备纳米乳，并对其理化性质进行了表征。
特性分析表明，粒径为 100.32±0.75nm，多分散指数为 0.18±0.01，Zeta 电位为-46.9±1.39mV，黏度为 1.24±0.34cps，渗透压为 285.33±0.58mOsm/kg，表明纳米乳具有适合肠胃外应用的兼容性。在 4°C 下储存 6 个月内，CLN 的理化性质稳定，透射电子显微镜显示 CLN 液滴几乎呈球形。CLN 的体外释放呈持续释放模式。CLN 的药代动力学特征表明，AUC 更高、半衰期延长、总血浆清除率降低，表明与无头孢呋辛治疗的大鼠相比，CLN 治疗的大鼠体内头孢呋辛的系统浓度更高。头孢呋辛在大脑中的生物分布也得到了类似的结果，CLN 表现出更高的 AUC、半衰期延长和清除率降低，与游离头孢呋辛溶液相比。
总体而言，CLN 表现出优异的理化性质，满足肠胃外给药的要求，并呈现出改善的体内药代动力学特征，这反映了其提高头孢呋辛向大脑输送的实际方法。
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