Lin Yi-Wen, Fang Chih-Hsiang, Liang Ya-Jyun, Yang Ching-Yun, Kuo Wei-Ting, Lin Feng-Huei
Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd, Taipei, 10617, Taiwan.
National Taiwan University Hospital, No.7, Chung Shan S. Rd., Zhongzheng Dist, Taipei City, 100225, Taiwan.
Biomater Res. 2023 Oct 5;27(1):98. doi: 10.1186/s40824-023-00432-4.
Alzheimer's disease is a neurodegenerative disorder, and Aβ aggregation is considered to be the central process implicated in its pathogenesis. Current treatments are faced by challenges such as serious side effects and reduced drug bioavailability. In this study, we developed a drug delivery system for intramuscular injection that uses cellular activity to achieve constant and long-term drug release.
Synthesized mesoporous hydroxyapatite (SHAP) was prepared via co-precipitation, and hydrophobic surface modification using stearic acid was then used to load clenbuterol by physical absorption, thus creating the drug delivery system. Clenbuterol release was achieved through cellular activity, with macrophage uptake triggering lysosome/endosome disruption, cytoplasmic release, extracellular exocytosis, and subsequent systemic circulation.
We found that clenbuterol-loaded SHAP enabled sustained release for more than 2 weeks and effectively modulated inflammation, reduced Aβ oligomer-induced toxicity, and prevented Aβ aggregation.
Our findings suggest that treatment with clenbuterol loaded in this SHAP delivery system could be a promising strategy for treating Alzheimer's disease.
阿尔茨海默病是一种神经退行性疾病，β淀粉样蛋白（Aβ）聚集被认为是其发病机制中的核心过程。当前的治疗面临着诸如严重副作用和药物生物利用度降低等挑战。在本研究中，我们开发了一种用于肌肉注射的药物递送系统，该系统利用细胞活性实现药物的持续和长期释放。
通过共沉淀法制备合成介孔羟基磷灰石（SHAP），然后使用硬脂酸进行疏水表面修饰，通过物理吸附加载克伦特罗，从而创建药物递送系统。克伦特罗通过细胞活性实现释放，巨噬细胞摄取触发溶酶体/内体破坏、细胞质释放、细胞外胞吐作用以及随后的全身循环。
我们发现载有克伦特罗的SHAP能够持续释放超过2周，并有效调节炎症、降低Aβ寡聚体诱导的毒性以及防止Aβ聚集。
我们的研究结果表明，用这种载有克伦特罗的SHAP递送系统进行治疗可能是治疗阿尔茨海默病的一种有前景的策略。
