Kumbhar Popat S, Kolekar Kaustubh Ajit, Vishwas Sukriti, Kamble Vikas, Bashir Bushra, Patil Kalpana S, Bhagwat Durgacharan, Gupta Guarav, Prasher Parteek, Singh Manisha, Singh Sachin Kumar, Disouza John, Patravale Vandana B
Department of Pharmaceutics, Tatyasaheb Kore College of Pharmacy, Warananagar, Dist: Kolhapur Maharashtra, Tal: Panhala, India, 416 113.
School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144 411, India.
Drug Deliv Transl Res. 2025 Jun 30. doi: 10.1007/s13346-025-01906-9.
Alzheimer's disease (AD) is the most prevalent and emerging neurodegenerative disease and serves as the seventh biggest cause of mortality across the globe. The pathogenesis of AD is linked with multiple hallmarks. The applications of anti-AD therapeutics approved by the FDA have been restricted because of the least permeability, bioavailability, negative effects, and huge cost. Various flavonoids have attenuated the potential pathogenic biomarkers of Alzheimer's disease (AD) and reduced disease progression. However, the presence of the blood-brain barrier (BBB), limited permeability, bioavailability, and low stability are chief concerns associated with their delivery against AD. Therefore, they have been loaded into various nanoformulations, including PLGA nanoparticles, gold nanoparticles, NLCs, exosomes, cell membrane-coated nanocarriers, and microneedles, to improve brain targeting and enhance therapeutic effects at the site of action. This review focuses on the flavonoid as a potential natural therapeutics against AD. Diverse flavonoids explored to manage AD are discussed with their multiple anti-AD mechanisms. AD pathophysiology, current treatment strategies and its challenges, and the significance of using flavonoids against AD are explained. Moreover, role of NSCs in AD and potential of flavonoids in targeting NSCs is briefed. Challenges in the delivery of flavonoids against AD and diverse ground-breaking nanotechnological strategies employed to deliver these flavonoid-based therapeutics are discussed with manifold case studies. Also, the mechanisms of transport of NCs are explained. Further, flavonoids in clinical trials are briefed with conclusions and future concerns. In conclusion, flavonoid-based therapeutics and their delivery using breakthrough nanotechnological approaches hold promise for successfully managing AD.
阿尔茨海默病（AD）是最常见且不断增多的神经退行性疾病，是全球第七大死因。AD的发病机制与多种特征相关。美国食品药品监督管理局（FDA）批准的抗AD疗法应用受到限制，原因在于其渗透性最差、生物利用度低、有副作用且成本高昂。多种黄酮类化合物已减轻了阿尔茨海默病（AD）潜在的致病生物标志物，并减缓了疾病进展。然而，血脑屏障（BBB）的存在、有限的渗透性、生物利用度以及低稳定性是其用于治疗AD时的主要问题。因此，它们已被载入各种纳米制剂中，包括聚乳酸-羟基乙酸共聚物纳米颗粒、金纳米颗粒、纳米脂质载体、外泌体、细胞膜包被纳米载体和微针，以改善脑靶向性并增强作用部位的治疗效果。 本综述聚焦于黄酮类化合物作为治疗AD的潜在天然疗法。探讨了用于治疗AD的多种黄酮类化合物及其多种抗AD机制。解释了AD的病理生理学、当前的治疗策略及其挑战，以及使用黄酮类化合物治疗AD的意义。此外，简要介绍了神经干细胞在AD中的作用以及黄酮类化合物靶向神经干细胞的潜力。讨论了黄酮类化合物用于治疗AD时的递送挑战以及用于递送这些基于黄酮类化合物的疗法的各种突破性纳米技术策略，并列举了多个案例研究。同时，解释了纳米载体的转运机制。此外，简要介绍了正在进行临床试验的黄酮类化合物，并给出了结论和未来关注点。总之，基于黄酮类化合物的疗法及其使用突破性纳米技术方法的递送有望成功治疗AD。
