Dimethysiloxane polymer for the effective transdermal delivery of donepezil in Alzheimer's disease treatment.

IF 5.8 3区医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Biomaterials Science Pub Date : 2024-11-22 DOI:10.1039/d4bm01368a

Jihyun Lee, In Gyoung Ju, Yeon-Jin Lim, Jin Hee Kim, Seungmin Lee, Yujin Choi, Myung Sook Oh, Jaehoon Kim, Dokyoung Kim

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Abstract

Donepezil (DNZ) has been used to treat dementia associated with mild, moderate, or severe Alzheimer's disease (AD). DNZ uptake can alleviate cognitive symptoms in AD patients via acetylcholinesterase (AChE) inhibition. However, oral administration of DNZ has limitations, including first-pass metabolism, difficulties with swallowing, and low patient compliance. In this work, we disclose a novel transdermal DNZ delivery system utilizing T2 polymer, synthesized via the ring-opening polymerization of 2,2,5,5-tetramethyl-2,5-disila-1-oxacyclopentane with trifluoroacetic acid (TFA). In the in vivo studies in an AD animal model, the DNZ-loaded T2 polymer (DNZ@T2) facilitated efficient transdermal DNZ delivery to the bloodstream and improved spatial working memory and long-term memory of the AD mouse model. Both the T2 polymer and DNZ@T2 exhibited low cytotoxicity and non-significant in vivo toxicity. This research highlights a promising transdermal delivery strategy for AD treatment, potentially enhancing therapeutic efficacy and patient compliance.

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二甲氧基硅氧烷聚合物用于在阿尔茨海默病治疗中有效透皮给药多奈哌齐。

多奈哌齐（DNZ）已被用于治疗与轻度、中度或重度阿尔茨海默病（AD）相关的痴呆症。多奈哌齐（DNZ）通过抑制乙酰胆碱酯酶（AChE）的吸收，可减轻阿尔茨海默病患者的认知症状。然而，口服 DNZ 有其局限性，包括首过代谢、吞咽困难和患者依从性低。在这项研究中，我们揭示了一种新型透皮 DNZ 给药系统，该系统利用 2,2,5,5- tetramethyl-2,5-disila-1-oxacyclopentane 与三氟乙酸 (TFA) 开环聚合合成的 T2 聚合物。在对一种注意力缺失症动物模型进行的体内研究中，负载 DNZ 的 T2 聚合物（DNZ@T2）促进了 DNZ 向血液的高效透皮输送，并改善了注意力缺失症小鼠模型的空间工作记忆和长期记忆。T2 聚合物和 DNZ@T2 均表现出较低的细胞毒性和不明显的体内毒性。这项研究强调了一种治疗注意力缺失症的前景广阔的透皮给药策略，有可能提高疗效和患者的依从性。

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来源期刊

Biomaterials Science MATERIALS SCIENCE, BIOMATERIALS-

CiteScore

11.50

自引率

4.50%

发文量

556

期刊介绍： Biomaterials Science is an international high impact journal exploring the science of biomaterials and their translation towards clinical use. Its scope encompasses new concepts in biomaterials design, studies into the interaction of biomaterials with the body, and the use of materials to answer fundamental biological questions.

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