<br>定制的鼻内水凝胶输送亚甲蓝可改善阿尔茨海默病的认知功能障碍,Advanced Materials

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定制的鼻内水凝胶输送亚甲蓝可改善阿尔茨海默病的认知功能障碍
Advanced Materials ( IF 27.4 ) Pub Date : 2024-02-23 , DOI: 10.1002/adma.202307081
Yujing Liu ₁ , Yun Tan ₂ , Guopan Cheng ₁ , Yaqiong Ni ₂ , Aihua Xie ₁ , Xiaozhen Zhu ₁ , Chao Yin ₂ , Yi Zhang ₂ , Tongkai Chen ₁

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过度磷酸化 tau 蛋白聚集体的积累是阿尔茨海默病 (AD) 的关键致病事件，并会诱导线粒体功能障碍和活性氧过度产生。然而，由于血脑屏障（BBB）的阻碍以及AD病理学的复杂性，AD的治疗仍然具有挑战性。鼻腔给药是绕过血脑屏障并将药物输送到大脑的有效方法。本研究以黑磷（BP）作为药物载体以及抗氧化剂，负载tau蛋白聚集抑制剂亚甲蓝（MB），得到BP-MB。对于鼻内 (IN) 递送，通过交联羧甲基壳聚糖和醛 Pluronic F127 (F127-CHO) 胶束制备热敏水凝胶。将BP-MB纳米复合材料掺入水凝胶中得到BP-MB@Gel。 BP-MB@Gel 可以鼻内注射，提供高鼻粘膜保留和受控药物释放。 IN给药后，BP-MB持续释放并输送至大脑，通过抑制tau神经病理学、恢复线粒体功能、减轻神经炎症发挥协同治疗作用，从而诱导AD小鼠模型的认知改善。这些发现凸显了在 AD 复杂病理学管理中大脑靶向药物输送的潜在策略。

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Customized Intranasal Hydrogel Delivering Methylene Blue Ameliorates Cognitive Dysfunction against Alzheimer's Disease

The accumulation of hyperphosphorylated tau protein aggregates is a key pathogenic event in Alzheimer's disease (AD) and induces mitochondrial dysfunction and reactive oxygen species overproduction. However, the treatment of AD remains challenging owning to the hindrance caused by the blood–brain barrier (BBB) and the complex pathology of AD. Nasal delivery represents an effective means of circumventing the BBB and delivering drugs to the brain. In this study, black phosphorus (BP) is used as a drug carrier, as well as an antioxidant, and loaded with a tau aggregation inhibitor, methylene blue (MB), to obtain BP-MB. For intranasal (IN) delivery, a thermosensitive hydrogel is fabricated by cross-linking carboxymethyl chitosan and aldehyde Pluronic F127 (F127-CHO) micelles. The BP-MB nanocomposite is incorporated into the hydrogel to obtain BP-MB@Gel. BP-MB@Gel could be injected intranasally, providing high nasal mucosal retention and controlled drug release. After IN administration, BP-MB is continuously released and delivered to the brain, exerting synergistic therapeutic effects by suppressing tau neuropathology, restoring mitochondrial function, and alleviating neuroinflammation, thus inducing cognitive improvements in mouse models of AD. These findings highlight a potential strategy for brain-targeted drug delivery in the management of the complex pathologies of AD.

更新日期：2024-02-23

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