Institute of Pharmaceutical Science, School of Cancer and Pharmaceutical Sciences, Faculty of Life Science and Medicine, King's College London, 150 Stamford street, London, SE1 9NH, UK.
Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK.
Adv Sci (Weinh). 2021 Jul;8(14):e2101058. doi: 10.1002/advs.202101058. Epub 2021 May 24.
This paper reports the use of a self-assembling hydrogel as a delivery vehicle for the Parkinson's disease drug l-DOPA. Based on a two-component combination of an l-glutamine amide derivative and benzaldehyde, this gel has very soft rheological properties and self-healing characteristics. It is demonstrated that the gel can be formulated to encapsulate l-DOPA. These drug-loaded gels are characterized, and rapid release of the drug is obtained from the gel network. This drug-loaded hydrogel has appropriate rheological characteristics to be amenable for injection. This system is therefore tested as a vehicle for nasal delivery of neurologically-active drugs-a drug delivery strategy that can potentially avoid first pass liver metabolism and bypass the blood-brain barrier, hence enhancing brain uptake. In vitro tests indicate that the gel has biocompatibility with respect to nasal epithelial cells. Furthermore, animal studies demonstrate that the nasal delivery of a gel loaded with H-labeled l-DOPA out-performed a simple intranasal l-DOPA solution. This is attributed to longer residence times of the gel in the nasal cavity resulting in increased blood and brain concentrations. It is demonstrated that the likely routes of brain penetration of intranasally-delivered l-DOPA gel involve the trigeminal and olfactory nerves connecting to other brain regions.
本文报告了一种自组装水凝胶作为帕金森病药物左旋多巴的递送载体的应用。该凝胶基于 l-谷氨酰胺酰胺衍生物和苯甲醛的两亲混合物，具有非常柔软的流变学特性和自修复特性。实验表明，该凝胶可以被用来包裹左旋多巴。对载药凝胶进行了特性分析，结果表明药物能够从凝胶网络中快速释放。这种载药水凝胶具有适宜的流变学特性，可用于注射。因此，该系统被测试为经鼻递送给神经活性药物的载体——一种药物递送策略，该策略可潜在地避免首过肝脏代谢和血脑屏障，从而增加大脑摄取。体外测试表明，该凝胶对鼻上皮细胞具有生物相容性。此外，动物研究表明，与简单的鼻内左旋多巴溶液相比，载有 H 标记的左旋多巴的凝胶的经鼻递送效果更好。这归因于凝胶在鼻腔中停留时间更长，导致血液和大脑中的浓度增加。研究表明，经鼻递送至大脑的左旋多巴凝胶的可能穿透途径涉及三叉神经和嗅觉神经，它们与其他大脑区域相连。
