Speedy Delivery: How Your Body’s Lymphatics Doubles as a Drug Delivery System

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Our bodies have two important transportation systems: the blood vessel system and the lymphatic vessel system. The blood vessel system is a closed circuit that connects to the heart, also known as the cardiovascular system.

The cells that make up the inner wall of blood vessels, called blood endothelial cells, are tightly connected. They allow only very small, water-loving molecules to pass through. Pushed by the heart, blood flows at high speed, carrying oxygen and nutrients to all parts of our body and removing waste products.

In contrast, the lymphatic vessels form an open-ended network. They carry a clear, watery liquid called lymph, which moves slowly. The cells that form the inner layer of lymphatic vessel walls, called lymphatic endothelial cells, overlap loosely and create button-like connections. These loose connections allow lymphatic vessels to collect extra water, larger proteins, debris, fats and immune cells from the body’s tissues. These are then drained into the blood vessel system. These unique features make the lymphatic system a potential target for treating various diseases.

Using Lymphatics for Treatment

Some genetic mutations or cancer treatments can cause issues in the lymphatic vessels, leading to a buildup of fluid, immune cells and large proteins in tissues and under the skin. This fluid accumulation causes swelling known as lymphedema. Currently, there are no prescription medicines approved by the U.S. Food and Drug Administration to treat lymphedema. However, research has shown that stimulating the growth of lymphatic vessels helps treat lymphedema.

Reactivating lymphatic vessels can also improve the success rate of treatments for cardiovascular diseases and transplanted organs. For example, some researchers have used gene therapy with specific substances called vascular endothelial growth factors to promote the growth of new lymphatic vessels and to treat lymphedema.

While activating lymphatic vessels can treat some diseases, this will only aggravate other conditions, such as lymphatic malformation and cancer that spreads throughout the body. In these cases, stopping lymphatic growth can significantly slow down disease progression and relieve pain.

Lymphatics as a Drug Delivery Route

Lymphatic vessels can also serve as a pathway for delivering medicines. Large, fatty molecules can’t enter the bloodstream and can only be transported through lymphatic vessels. Lymphatic capillaries in the small intestine play a crucial role in absorbing fats in our body. We can take oral medications that dissolve in fat because our lymphatic vessels absorb them. Medications made up of smaller molecules—that are still too large to enter the bloodstream—can be given through injection. These medicines are picked up by lymphatic vessels through their button-like connections, which allows drug levels in the lymph and bloodstream to remain stable while it fights disease.

Lymphatics play a significant role in many physiological conditions. Harnessing the lymphatic vessels’ ability to collect fluid, debris and fats can help researchers design drug delivery systems to help people use medicines more effectively.

Yanna Tian, PhD, is a postdoctoral associate at University of North Carolina at Chapel Hill. Her current research focuses on the role of adrenomedullin signaling pathways in the cardiovascular and lymphatic vascular systems.

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