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

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 <i>via</i> 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 <i>via</i> the ring-opening polymerization of 2,2,5,5-tetramethyl-2,5-disila-1-oxacyclopentane with trifluoroacetic acid (TFA). In the <i>in vivo</i> 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 <i>in vivo</i> toxicity. This research highlights a promising transdermal delivery strategy for AD treatment, potentially enhancing therapeutic efficacy and patient compliance.