Biomacromolecules are increasingly important for treating major diseases such as tumors, infections, cardiovascular diseases, metabolic disorders, and autoimmune conditions. However, their administration relies heavily on injections, which cause pain, generate medical waste, and lead to poor patient compliance. Microneedles, as a novel delivery system, penetrate the stratum corneum to enable efficient and minimally invasive intradermal drug delivery, demonstrating significant clinical potential.
A recent review by a collaborative team from Sun Yat-sen University and Jinan University systematically summarizes the latest advances in biomacromolecule-loaded microneedles for treating various major diseases. The article details the design of functional microneedles with specific structures to overcome drug delivery barriers in the skin, heart, and blood vessels, thereby improving therapeutic outcomes. It also discusses key challenges in industrial-scale manufacturing and clinical translation, proposing forward-looking solutions.
“Microneedle technology is not limited to transdermal delivery; with advances in biomaterials and tissue engineering, its applications have expanded to oral and cardiovascular tissues, showing broad potential,” said corresponding author Xin Pan. “We believe that through rational design, microneedles are poised to become a mainstream platform for next-generation biomacromolecule delivery.”
Dr. Xin Pan is a professor in the School of Pharmaceutical Sciences at Sun Yat-sen University, and Dr. Tingting Peng is an associate professor in the College of Pharmacy at Jinan University.
Multiple Advantages of Microneedles
Microneedles typically consist of micron-scale needle arrays and a baseplate, offering significant advantages over conventional injections and transdermal patches: microneedles penetrate the stratum corneum to create microchannels that significantly enhance the delivery efficiency of biomacromolecules. Their administration bypasses dermal pain receptors, enabling a painless experience and allowing for self-administration. Furthermore, therapeutics loaded within microneedles are maintained in a solid state, which improves their stability and simplifies storage and transportation. This approach also minimizes the generation of medical sharps waste, offering a particular advantage in resource-limited settings.
Smart Responsiveness and Controlled Release
The researchers highlight that smart microneedle systems with pH, enzyme, or photothermal responsiveness can achieve on-demand drug release and sustained action. For instance, in cancer immunotherapy, a pH-responsive microneedle encapsulates PD-1 inhibitors inside dextran nanoparticles that disintegrate specifically in the acidic tumor microenvironment. This design allows for controlled drug release, significantly enhances T-cell infiltration, and effectively suppresses tumor growth. In the treatment of thrombotic diseases, an enzyme-responsive microneedle modified with thrombin-cleavable peptides can intelligently trigger the on-demand release of heparin directly at the thrombus site, resulting in long-term and autonomous anticoagulation regulation.
Overcoming Industrial Translation Bottlenecks
Despite rapid technological progress, the large-scale production and clinical application of microneedles face challenges such as low drug loading, non-standardized manufacturing processes, and unverified long-term safety. The authors suggest that optimizing needle geometry, material composition, and fabrication processes (e.g., 3D printing, centrifugal perfusion), combined with nano-encapsulation technologies, can effectively improve drug loading and stability. Furthermore, establishing standards compliant with Good Manufacturing Practice is crucial for translating microneedle products from the laboratory to the clinic.
“The integration of microneedles with artificial intelligence, functional biomaterials, and advanced sensing technologies is driving their evolution toward intelligent and personalized systems,” added researcher Tingting Peng. “Future innovations, such as microneedle robots and biomimetic microneedles, will further expand their applications in intractable disease treatment.”
The review comprehensively outlines recent applications of microneedles in infectious disease vaccination, tumor immunotherapy, cardiovascular repair, metabolic regulation, and autoimmune disease treatment, providing a valuable reference for the development and clinical translation of biomacromolecule-loaded microneedle formulations.
The complete study is accessible via DOI:10.34133/research.0879