Nose-to-brain delivery of drug nanocrystals by using Ca2+ responsive deacetylated gellan gum based in situ-nanogel
Nose-to-brain delivery of drug nanocrystals by using Ca2+ responsive deacetylated gellan gum based in situ-nanogel
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DOI：
10.1016/j.ijpharm.2020.120182
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发表时间：
2021-01-05
影响因子：
5.8
通讯作者：
Wang, Changhong
中科院分区：
文献类型：
--
作者：
Huang, Guiting;Xie, Jin;Wang, Changhong
本研究的目的是使用碳水化合物聚合物脱乙酰结冷胶（DGG）作为基质，设计基于纳米晶的鼻内原位凝胶（IG），用于鼻-脑给药。以去氢骆驼蓬碱为模型药物，采用均质-喷雾干燥耦合技术制备了去氢骆驼蓬碱纳米晶。HAR-NC在DGG溶液中再分散，形成离子触发的去氢骆驼蓬碱纳米晶原位凝胶（HAR-NC-IG）。在均质和喷雾干燥过程中，HAR的结晶状态保持不变。当DGG含量为0.5%时，HAR-NC-IG具有良好的原位凝胶化能力、保水性和体外释药性能。鼻内给药HAR-NC-IG的脑内生物利用度是口服HARNC的25倍，这可能归因于HAR-NC的纳米化效应和鼻液引发的DGG的生物粘附特性。HAR-NC-IG能显著抑制脑内乙酰胆碱酯酶（AchE）的表达，提高脑内乙酰胆碱（ACh）的含量（p < 0.01）。DGG基纳米胶囊原位凝胶可延长难溶性药物在脑内的滞留时间，提高药物在脑内的生物利用度，是一种很有前途的难溶性药物鼻-脑给药载体。
The objective of this study is to use a carbohydrate polymer deacetylated gellan gum (DGG) as matrix to design nanocrystals based intranasal in situ gel (IG) for nose-to -brain delivery of drug. The harmine nanocrystals (HARNC) as model drug were prepared by coupling homogenization and spray-drying technology. The HAR-NC was redispersed in the (DGG) solutions and formed the ionic-triggered harmine nanocrystals based in situ gel (HAR-NC-IG). The crystal state of HAR remained unchanged during the homogenization and spray-drying. And the HAR-NC-IG with 0.5% DGG exhibited excellent in situ-gelation ability, water retention property and in vitro release behavior. The bioavailability in brain of intranasal HAR-NC-IG were 25-fold higher than that of oral HARNC, which could be attributed to nanosizing effect of HAR-NC and bioadhesive property of DGG triggered by nasal fluid. And the HAR-NC-IG could significantly inhibit the expression of acetylcholinesterase (AchE) and increase the content of acetylcholin (ACh) in brain compared with those of reference formulations (p < 0.01). The DGG based nanocrystals-in situ gel was a promising carrier for nose-to-brain delivery of poorly soluble drug, which could prolong the residence time and improve the bioavailability of poorly soluble drugs in brain.