Hydrogel-forming Microneedles: A Next-generation Approach for Enhanced Dermal Drug Delivery in Alzheimer's and Neurological Disorders.

Hydrogel-Forming Microneedles (HFMNs) offer a minimally invasive, patient-friendly, and sustained-release platform for transdermal delivery. By swelling upon insertion to form a hydrogel matrix, they enable efficient delivery of small molecules, biologics, and nanoparticles while bypassing gastrointestinal degradation and first-pass metabolism. In neurological disorders such as Alzheimer's and Parkinson's disease, they can improve bioavailability and overcome Blood-Brain Barrier (BBB) restrictions. However, limitations remain, including limited macromolecule payload, variable skin penetration, and regulatory challenges. To critically review recent progress in HFMNs for neurological drug delivery and assess their translational readiness. The objective is to evaluate advances in design, materials, fabrication, and therapeutic applications, and identify key challenges and future prospects. A literature review (2018-2024) covering polymer selection, crosslinking strategies, smart-material integration, and CNS-targeted applications. HFMNs successfully deliver donepezil, memantine, rivastigmine, and neurotrophic factors, achieving sustained release, improved bioavailability, and enhanced patient compliance. Smart HFMNs with biosensors and nanocarriers show improved BBB penetration. HFMNs represent a promising alternative to conventional CNS drug delivery. Addressing payload, penetration consistency, and scalable manufacturing will be vital for clinical adoption.