Microneedle (MN) technologies have emerged as a groundbreaking platform for transdermal and intradermal drug delivery, offering a minimally invasive alternative to oral and parenteral routes. Unlike passive transdermal systems, MNs allow the permeation of hydrophilic macromolecules, such as peptides, proteins, and vaccines, by penetrating the stratum corneum barrier without causing pain or tissue damage, unlike hypodermic needles. Recent advances in materials science, microfabrication, and biomedical engineering have enabled the development of various MN types, including solid, coated, dissolving, hollow, hydrogel-forming, and hybrid designs. Each type has unique mechanisms, fabrication techniques, and pharmacokinetic profiles, providing customized solutions for a range of therapeutic applications. The integration of 3D printing technologies and stimulus-responsive polymers into MN systems has enabled patches that combine drug delivery with real-time physiological sensing. Over the years, MN applications have grown beyond vaccines to include the delivery of insulin, anticancer agents, contraceptives, and various cosmeceutical ingredients, highlighting the versatility of this platform. Despite this progress, broader clinical and commercial adoption is still limited by issues such as scalable and reliable manufacturing, patient acceptance, and meeting regulatory expectations. Overcoming these barriers will require coordinated efforts across engineering, clinical research, and regulatory science. This review thoroughly summarizes MN technologies, beginning with their classification and drug-delivery mechanisms, and then explores innovations, therapeutic uses, and translational challenges. It concludes with a critical analysis of clinical case studies and a future outlook for global healthcare. By comparing technological progress with regulatory and commercial hurdles, this article highlights the opportunities and limitations of MN systems as a next-generation drug-delivery platform.

Nanobodies (single-domain antibodies, VHHs) have emerged as versatile tools for evaluating and treating Alzheimer’s disease (AD). They offer distinct engineering benefits compared with traditional antibodies and small molecules, including small size, stability, and specificity. In AD, nanobodies have been shown in preclinical models to neutralize toxic amyloid-β oligomers, inhibit tau generation and aggregation, and modulate neuroinflammation, thereby demonstrating significant therapeutic potential. However, all nanobody applications in AD are discussed strictly as preclinical therapeutic potential rather than established clinical therapies, and direct clinical evidence in patients with AD is still lacking. Advanced engineering strategies, including intranasal and intrathecal routes, receptor-mediated transport, plasma protein binding with albumin, and focused ultrasound to facilitate brain penetration. Additionally, to improve nanobody delivery precision, half-life, and efficacy, strategies such as integrating nanobodies with nanoparticles, dendrimers, liposomes, and viral vectors are being employed. In fact, nanobodies are applied beyond monotherapy across multiple technological platforms to optimize brain delivery and target multiple targets. Nanobodies have been used on bispecific and trispecific antibody platforms, as well as in CRISPR/Cas9 editing and AI-driven technologies, to expand their applications. Recently, preclinical evidence has been mounting on the efficacy of nanobodies in clearing Aβ and tau, preserving synapses, and normalizing biomarkers. Comparison with FDA-approved anti-Aβ monoclonal antibodies (aducanumab, lecanemab, and donanemab) highlights opportunities and current translational gaps, including safety testing, half-life extension, and delivery optimization. This review critically delineates the current molecular mechanisms, emerging strategies, and delivery platforms, and emphasizes the potential of nanobodies as promising therapeutic and diagnostic molecules in AD therapeutics.

Microneedle (MN) technologies have emerged as a groundbreaking platform for transdermal and intradermal drug delivery, offering a minimally invasive alternative to oral and parenteral routes. Unlike passive transdermal systems, MNs allow the permeation of hydrophilic macromolecules, such as peptides, proteins, and vaccines, by penetrating the stratum corneum barrier without causing pain or tissue damage, unlike hypodermic needles. Recent advances in materials science, microfabrication, and biomedical engineering have enabled the development of various MN types, including solid, coated, dissolving, hollow, hydrogel-forming, and hybrid designs. Each type has unique mechanisms, fabrication techniques, and pharmacokinetic profiles, providing customized solutions for a range of therapeutic applications. The integration of 3D printing technologies and stimulus-responsive polymers into microneedle systems has opened the door for patches that pair drug delivery with real-time physiological sensing. Over the years, microneedle applications have grown beyond vaccines to include the delivery of insulin, anticancer agents, contraceptives, and various cosmeceutical ingredients, highlighting the versatility of this platform. Despite this progress, broader clinical and commercial adoption is still limited by issues such as scalable and reliable manufacturing, patient acceptance, and meeting regulatory expectations. Overcoming these barriers will require coordinated efforts across engineering, clinical research, and regulatory science. This review thoroughly summarizes MN technologies, beginning with their classification and drug-delivery mechanisms, and then explores innovations, therapeutic uses, and translational challenges. It concludes with a critical analysis of clinical case studies and a future outlook for global healthcare. By comparing technological progress with regulatory and commercial hurdles, this article highlights the opportunities and limitations of MN systems as a next-generation drug-delivery platform.

Nanobodies (single-domain antibodies, VHHs) have emerged as versatile tools for evaluating and treating Alzheimer’s disease (AD). They offer unique advantages over traditional antibodies and small molecules, including small size, stability, and specificity. In AD, nanobodies were used to neutralize toxic amyloid-β oligomers, inhibit tau generation and aggregation, and modulate neuroinflammation, thereby demonstrating significant therapeutic potential. The delivery of nanobodies requires advanced strategies, including intranasal and intrathecal routes, receptor-mediated transport, plasma protein binding with albumin, and focused ultrasound to facilitate brain penetration. Additionally, to improve nanobody delivery precision, half-life, and efficacy, strategies such as integrating nanobodies with nanoparticles, dendrimers, liposomes, and viral vectors are being employed. In fact, nanobodies are applied beyond monotherapy across multiple technological platforms to optimize brain delivery and target multiple targets. Nanobodies have been used on bispecific and trispecific antibody platforms, as well as in CRISPR/Cas9 editing and AI-driven technologies, to expand their applications. Recently, preclinical evidence has been mounting on the efficacy of nanobodies in clearing Aβ and tau, preserving synapses, and normalizing biomarkers. Notably, clinical trials of bispecific antibodies, including trontinemab, are signaling translational progress and regulatory approvals, and further support would validate this class of therapeutic molecules. This review critically delineates the current molecular mechanisms, emerging strategies, and delivery platforms, and emphasizes the potential of nanobodies as promising therapeutic and diagnostic molecules in AD therapeutics.