Evaluation of Brain Targeting and Mucosal Integrity of Nasally Administrated Nanostructured Carriers of a CNS Active Drug, Clonazepam
Evaluation of Brain Targeting and Mucosal Integrity of Nasally Administrated Nanostructured Carriers of a CNS Active Drug, Clonazepam
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DOI：
10.18433/j30s31
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发表时间：
2013-01-01
影响因子：
2.7
通讯作者：
Mortada, Nahed Daoud
中科院分区：
文献类型：
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作者：
Abdel-Bar, Hend Mohamed;Abdel-Reheem, Amal Youssef;Mortada, Nahed Daoud
目得：该研究的目的是通过使用具有已证明安全性的纳米载体的非侵入性鼻内（内）途径将氯硝西泮（CNS活性药物）靶向至脑。方法：通过将肉豆蔻酸异丙酯、吐温80、Cremophor EL或卵磷脂、聚乙二醇200、丙二醇或乙醇以不同比例与水混合来制备氯硝西泮纳米载体。通过各种方法进行纳米载体的体外表征，包括：偏振光显微镜、粒度测定、粘度测量和药物释放研究。进行了比较鼻内和静脉内给药的体内研究。计算药物靶向效率（DTE %）和直接鼻脑转运百分比（DTP %），并进行鼻腔完整性评估。研究结果：所获得的制剂具有低于100 nm的粒度，有利于快速直接鼻至脑转运，并且100%药物释放的时间（T-100%）取决于系统组成。氯硝西泮纳米结构载体的血浆Tmax在10-30分钟之间变化，脑Tmax不超过10 min，静脉注射30 min。尽管不同测试的纳米载体和静脉内纳米载体的血浆AUC（0-无穷大）之间没有显著差异（p>0.05），但与静脉内施用相比，不同鼻用制剂的脑AUC（0-无穷大）增加（3.6 - 7.2倍）证实了经由嗅觉区域的直接鼻至脑转运。此外，DTE和DTP%证实了鼻内给药后氯硝西泮的脑靶向作用。结论：结果证实，鼻内纳米载体被证明是氯硝西泮静脉给药的安全替代方案，具有快速的鼻-脑转运。
PURPOSE: The aim of the study was to target clonazepam, a CNS active drug, to the brain through the non-invasive intranasal (in) route using of nanocarriers with proven safety METHOD: in clonazepam nanocarriers were prepared by mixing isopropyl myristate, Tween 80, Cremophor EL or lecithin, polyethylene glycol 200, propylene glycol or ethanol in different ratios with water. in-vitro characterization of the nanocarriers was done by various methods including: polarized light microscopy, particle size determination, viscosity measurements and drug release studies. in-vivo study comparing intranasal and intravenous administration was performed. The drug targeting efficiency (DTE %) and direct nose to brain transport percentage (DTP %) were calculated and nasal integrity assessment was carried out. RESULTS: The obtained formulae had particle size below 100 nm favoring rapid direct nose to brain transport and the time for 100% drug release (T-100%) depended on systems composition. Plasma T-max of clonazepam nanostructured carriers varied from 10-30 min., while their brain Tmax did not exceed 10 min, in comparison with 30 min for iv solution. Although there was no significant difference (p>0.05) between the plasma AUC(0-infinity) of the different tested nanocarriers and intravenous one, the increase in brain AUC(0-infinity) of different nasal formulations in comparison to that of iv administration (3.6 -7.2 fold) confirms direct nose to brain transport via olfactory region. Furthermore, DTE and DTP% confirmed brain targeting of clonazepam following intranasal administration. CONCLUSION: The results confirmed that intranasal nanocarriers were proved to be safe alternative for iv clonazepam delivery with rapid nose to brain transport.