Anti-Aggregation System for the Enhanced Transdermal Delivery of Cell Membrane-Coated Nanoparticles

Biomimetic nanoparticles such as cell membrane-coated nanoparticles (CMNPs) are widely used for the <i>in vivo</i> treatment of various diseases because they offer a high targeting efficiency, excellent biocompatibility, immune evasion capability, and longer circulation times. However, current noninvasive delivery strategies for CMNPs often face limitations regarding maintaining optimal coating stability and distribution efficiency. In this study, we develop a platform for the transdermal delivery of CMNPs as a noninvasive alternative to injections. Specifically, an antiaggregation transdermal delivery tool (AATDT) was developed using biocompatible beeswax and hyaluronic acid. The proposed system reduced the surface energy of the CMNPs, thus preventing aggregation in the liquid phase and promoting skin permeation via enhanced hydration effects. The CMNPs were delivered to a depth of over 500 μm into the skin tissue without aggregation or systemic toxicity. The proposed AATDT thus offers a versatile, clinically translatable strategy for enhancing the stability and delivery efficiency of CMNPs in noninvasive therapeutic applications.