Exploring heart lymphatics in local drug delivery

Area of Science:

• Cardiovascular Research
• Biomedical Engineering
• Regenerative Medicine

Background:

• Local intramyocardial delivery (IMD) is crucial for cell and gene therapies targeting heart failure and coronary artery disease.
• Understanding agent migration post-IMD is vital for optimizing therapeutic efficacy and safety.
• Lymphatic pathways represent a significant route for agent redistribution from the myocardium.

Purpose of the Study:

• To characterize the migration patterns of locally delivered agents within the heart.
• To investigate the role of lymphatic vessels in the redistribution of intramyocardial injections.
• To determine the influence of particle size on the localization of intramyocardial therapies.

Main Methods:

• Injection of fluorescent microspheres (20 nm to 15,000 nm) into the left ventricular wall of rats (N=83).
• Utilizing fluorescent microscopy to visualize and quantify microsphere migration patterns.
• Assessing the presence of microspheres in cardiac lymph nodes and lymphatic networks.

Main Results:

• Microspheres <200 nm widely distributed within cardiac lymphatics and the ventricular wall.
• Cardiac lymph nodes were identified only with 20 nm and 100 nm microsphere deliveries.
• Microspheres ≥15,000 nm showed no significant migration from the injection site.

Conclusions:

• Tortuous lymphatic pathways facilitate the migration of small agents from intramyocardial delivery sites.
• IMD's lymphatic role may support therapeutic angiogenesis and collateral formation.
• The retention of large particles suggests IMD's potential for localized, long-term cell therapy delivery.