Minimally invasive snakebite inspired microneedle delivery system for internal organs

Efficient distribution of therapeutics to the targeted site, particularly internal organs, is essential for their therapeutic success. Here, we developed a therapeutic delivery system targeting internal organs, which features a mechanism akin to a snake's jaw for grasping and deploying detachable microneedles (MNs) embedded with therapeutics. This solves the current challenges of delivering microneedle patches without open chest or abdominal wall surgery. We showed an example of this technology via delivering exosomes derived from mesenchymal stem cells (MSCs) directly to the heart's damaged regions via percutaneous minimally invasive surgery. The shell of MNs is fabricated from methacrylated hyaluronic acid (MeHA), which ensures mechanical strength for myocardium penetration, while the hyaluronic acid (HA) core allows a sustained release of exosomes. In a rat model of myocardial infarction (MI), the delivery of exosomes-loaded microneedles (XOs-MNs) resulted in angiomyogenesis and promoted cardiac function. The feasibility of this microneedle delivery method was also confirmed in a pig model. With its capability to encapsulate a wide range of therapeutic formulations, our system presents a versatile platform for the minimally invasive administration of treatments to internal organs.