Enhanced brain targeting of curcumin by intranasal administration of a thermosensitive poloxamer hydrogel
Enhanced brain targeting of curcumin by intranasal administration of a thermosensitive poloxamer hydrogel
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DOI：
10.1111/jphp.12043
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发表时间：
2013-06-01
影响因子：
3.3
通讯作者：
Yang, Yilin
中科院分区：
文献类型：
--
作者：
Chen, Xi;Zhi, Feng;Yang, Yilin
目的研制姜黄素鼻用温敏水凝胶，提高其脑靶向性。方法考察凝胶化温度、凝胶化时间、药物释放特性、黏膜纤毛毒性以及大鼠鼻-脑转运特性。关键发现由Pluronic F127和泊洛沙姆188组成的开发的鼻水凝胶具有较短的凝胶化时间，较长的粘膜纤毛运输时间，并在体温下在大鼠鼻腔中产生较长的姜黄素保留。通过透析膜法评价水凝胶的释药机制为扩散控制释药，而通过无膜法评价时为溶解控制释药。粘膜纤毛毒性研究表明，该水凝胶可保持鼻粘膜完整性，直至应用后14天。姜黄素水凝胶鼻内给药后药物在大脑、小脑、海马和嗅球中的靶向效率分别是姜黄素溶液注射液静脉给药后的1.82、2.05、2.07和1.51倍，表明水凝胶显著增加了姜黄素在大鼠脑组织中的分布，尤其是小脑和海马体结论研制的姜黄素温敏鼻用凝胶剂具有良好的凝胶性、释药特性、生物安全性和脑吸收效率。
Objectives The aim of this study was to develop a curcumin intranasal thermosensitive hydrogel and to improve its brain targeting efficiency. Methods The hydrogel gelation temperature, gelation time, drug release and mucociliary toxicity characteristics as well as the nose-to-brain transport in the rat model were evaluated. Key findings The developed nasal hydrogel, composed of Pluronic F127 and Poloxamer 188, had shorter gelation time, longer mucociliary transport time and produced prolonged curcumin retention in the rat nasal cavity at body temperature. The hydrogel release mechanism was diffusion-controlled drug release, evaluated by the dialysis membrane method, but dissolution-controlled release when evaluated by the membraneless method. A mucociliary toxicity study revealed that the hydrogel maintained nasal mucosal integrity until 14 days after application. The drug-targeting efficiencies for the drug in the cerebrum, cerebellum, hippocampus and olfactory bulb after intranasal administration of the curcumin hydrogel were 1.82, 2.05, 2.07 and 1.51 times that after intravenous administration of the curcumin solution injection, respectively, indicating that the hydrogel significantly increased the distribution of curcumin into the rat brain tissue, especially into the cerebellum and hippocampus. Conclusions A thermosensitive curcumin nasal gel was developed with favourable gelation, release properties, biological safety and enhanced brain-uptake efficiency.