Minimally invasive snakebite inspired microneedle delivery system for internal organs

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Drug Delivery Systems

Background:

• Efficient therapeutic delivery to internal organs is crucial for treatment success but often requires invasive surgery.
• Current microneedle (MN) technologies are primarily limited to transdermal applications, posing challenges for internal organ targeting.
• Minimally invasive approaches are highly desirable for treating internal organ conditions.

Purpose of the Study:

• To develop and validate a novel microneedle (MN) delivery system for targeted therapeutic administration to internal organs.
• To demonstrate the system's capability in delivering mesenchymal stem cell-derived exosomes (MSCs) to damaged cardiac tissue.
• To assess the therapeutic efficacy of this delivery method in preclinical models.

Main Methods:

• A snake-jaw-inspired mechanism was engineered for grasping and deploying detachable microneedles (MNs).
• Microneedles were fabricated with a methacrylated hyaluronic acid (MeHA) shell for penetration and a hyaluronic acid (HA) core for sustained release.
• Exosomes derived from mesenchymal stem cells (MSCs) were loaded into the MNs (XOs-MNs) for cardiac delivery.
• The system's feasibility and efficacy were tested in rat myocardial infarction models and confirmed in a pig model via percutaneous minimally invasive surgery.

Main Results:

• The developed MN system successfully achieved percutaneous delivery of therapeutics to internal organs, specifically the heart.
• In a rat myocardial infarction model, XOs-MNs promoted angiomyogenesis and improved cardiac function.
• The microneedle delivery method was validated in a pig model, demonstrating its broad applicability.
• The MeHA shell provided mechanical integrity for myocardial penetration, while the HA core ensured sustained exosome release.

Conclusions:

• The snake-jaw-inspired microneedle delivery system offers a versatile platform for minimally invasive treatment of internal organs.
• This technology overcomes the limitations of surgical interventions for internal organ therapies.
• The system holds significant potential for delivering various therapeutic formulations, including exosomes, to target sites for enhanced efficacy.