Dissolving microneedle patch integrated with microparticle depots for sustained intradermal delivery of donepezil

Alzheimer's Disease (AD) is a significant global health challenge worldwide and imposes a substantial economic burden. Due to the shortcomings of conventional pharmaceutical formulations (e.g., tablet and microparticle depot injection), such as low bioavailability, frequent dosing, and the inconvenience related to injection), there is a pressing need to develop a convenient and effective medical cue for AD treatment. Here, a hybrid dissolving microneedle patch integrated with donepezil (DNP)-encapsulated biodegradable microparticle depots is introduced for sustained DNP delivery, reduced dosing frequency, and improved patient compliance. Once the microneedle patch delivers DNP-encapsulated microparticle depots into the skin, they subsequently act as drug reservoirs for the sustained release of the DNP for over 2 weeks. In vitro and ex vivo insertion experiments showed that the microneedle patches could provide enough mechanical strength and good morphology, as well as enhanced dissolvability and retention of microparticle depots in the skin. In vitro cytocompatibility study in NIH3T3 cells demonstrated the biocompatibility of the materials comprising microneedle patch. This hybrid system offers a promising alternative to conventional oral or injectable therapies for AD by enabling self-administrable, pain-free, and long-acting transdermal delivery.