聚合物凝胶混悬液中褪黑素的经鼻向脑转运：大鼠的微透析研究。

Nose-to-brain transport of melatonin from polymer gel suspensions: a microdialysis study in rats.

机构信息

Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA.

出版信息

J Drug Target. 2011 Nov;19(9):731-40. doi: 10.3109/1061186X.2011.558090. Epub 2011 Mar 23.

DOI:10.3109/1061186X.2011.558090

PMID:21428693

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3334865/

Abstract

PURPOSE

Exogenous melatonin (MT) has significant neuroprotective roles in Alzheimer's and Parkinson's diseases. This study investigates the delivery MT to brain via nasal route as a polymeric gel suspension using central brain microdialysis in anesthetized rats.

METHODS

Micronized MT suspensions using polymers [carbopol, carboxymethyl cellulose (CMC)] and polyethylene glycol 400 (PEG400) were prepared and characterized for nasal administration. In vitro permeation of the formulations was measured across a three-dimensional tissue culture model EpiAirway(™). The central brain delivery into olfactory bulb of nasally administered MT gel suspensions was studied using brain microdialysis in male Wistar rats. The MT content of microdialysis samples was analyzed by high performance liquid chromatography (HPLC) using electrochemical detection. The nose-to-brain delivery of MT formulations was compared with intravenously administered MT solution.

RESULTS

MT suspensions in carbopol and CMC vehicles have shown significantly higher permeability across Epiairway(™) as compared to control, PEG400 (P < 0.05). The brain (olfactory bulb) levels of MT after intranasal administration were 9.22, 6.77 and 4.04-fold higher for carbopol, CMC and PEG400, respectively, than that of intravenous MT in rats. In conclusion, microdialysis studies demonstrated increased brain levels of MT via nasal administration in rats.

摘要

目的

外源性褪黑素（MT）在阿尔茨海默病和帕金森病中具有显著的神经保护作用。本研究通过麻醉大鼠的中枢脑微透析，研究了通过鼻途径将 MT 递送至大脑的方法，即作为聚合物凝胶混悬剂。

方法

使用聚合物（卡波姆、羧甲基纤维素（CMC））和聚乙二醇 400（PEG400）制备并微粉化 MT 混悬剂，并对其进行了鼻内给药的特征描述。通过三维组织培养模型 EpiAirway(™) 测量了制剂的体外渗透情况。使用脑微透析研究了经鼻给予 MT 凝胶混悬剂后，MT 向嗅球的中枢脑传递情况。通过高效液相色谱（HPLC）电化学检测法分析微透析样品中的 MT 含量。将 MT 制剂的鼻内至脑递送与静脉内给予 MT 溶液进行了比较。

结果

与对照、PEG400 相比，卡波姆和 CMC 载体中的 MT 混悬剂在 Epiairway(™) 中的渗透性显著更高（P < 0.05）。与静脉内给予 MT 相比，经鼻给予后，大鼠脑（嗅球）中的 MT 水平分别提高了 9.22、6.77 和 4.04 倍。总之，微透析研究表明，通过鼻内给药可提高大鼠大脑中的 MT 水平。