Recent Advances in Nanotechnology‐Mediated Noninvasive Transdermal and Topical Delivery of Proteins

Protein therapeutics are emerging as essential technologies due to their functional and chemical properties. However, their application is currently limited to delivery by oral and injection methods—the former being inefficient and the latter invasive and potentially tissue damaging. Researchers are, therefore, exploring noninvasive delivery systems for proteins through the skin, including transdermal and topical delivery. The large molecular size of proteins presents a key challenge for skin penetration, hindering their ability to penetrate the dense skin lamellar structure. This review focuses on using nanoparticles as carriers to increase protein stability and enhance skin penetration. The use of noninvasive or minimally invasive enhancers for controlling and improving penetration depth is also examined. Furthermore, the physical properties of nanoparticles that affect delivery are evaluated, aiming to propose ways to advance transdermal and topical delivery methods in the future. Protein transdermal and topical delivery face significant hurdles due to the large size of proteins and the dense skin layer. Nanoparticle‐guided delivery is an emerging technology designed to increase protein stability and skin penetration. The control and enhancement of penetration by combining enhancers with nanoparticles have been analyzed. Moreover, the physical properties of nanoparticles that affect delivery have been examined.