Structure Of Lymph Node

Recently, liposomes have received much attention as lymph-node drug-delivery agents. This interest in the development of new methods of lymph-node drug-delivery stems from the increasing awareness of the importance of lymph nodes in cancer prognosis, their importance for vaccine immune stimulation and the realization that the lymph nodes harbor human immunodeficiency virus (HIV) as well as other infectious disease (1-4). New methods of delivering drugs and antigens to lymph nodes are currently under investigation.

The lymphatic system consists of a network of lymphatic vessels and lymph nodes that serve as a secondary vascular system to return fluid that leaks from the blood vessels in the extremities and other organs back to the vasculature (5). The lymphatic system also moves substantial volumes of fluid from the peritoneal cavity and pleural cavity back into the blood circulation.

Lymph fluid originating from the interstitial spaces between tissue cells and from within the body's cavities moves into lymphatic capillaries through lymph nodes and back into the blood circulation. Lymph fluid of different organs and the body's extremities in addition to body cavities is collected by large lymphatic trunks that feed into one of two lymphatic ducts: the thoracic duct and right lymphatic duct. From these ducts, the lymph fluid then returns to the bloodstream through veins in the neck region (internal jugular and subclavian veins) (6,7).

The lymphatic vessels also serve as a major transport route for antigens, microorganisms, immune cells, and disseminating tumor cells along with interstitial macromolecules that have gained entry to the interstitial space (8). The lymphatic vessels are traversed by immune cells such as dendritic cells, macrophages, and, as their name reveals, lymphocytes. As a part of this system that recycles fluid from the interstitial spaces and the body's cavity back to the arteriovenous vascular system, the lymph nodes are ideally positioned to serve as surveillance organs to monitor microbial invasion and to defend the body against these invading microorganisms.

Liposomes are ideal structures for delivering therapeutic agents to the lymph nodes. Their ideal features are based on their size, which prevents their direct absorption into the blood, the large amount of drugs and other therapeutic agents that liposomes can carry, and their biocompatibility.

Although liposomes are too large to be directly absorbed into the bloodstream, they are small enough to enter the lymphatic vessels and lymph nodes following subcutaneous (SC) injection, intradermal injection, intramuscular injection, injection directly into organs or tumors, and injection into the body's cavities. Following SC injection or other injection directly into tissue, it appears that a certain portion of liposomes are taken up locally and retained for a prolonged time, whereas another portion of the liposomes are cleared from this local site and move into the lymphatic vessels where they can be trapped in lymph nodes or else move completely through the lymphatic system and return to the blood at the thoracic duct.

Lymphatic fluid enters the lymph node through the afferent lymphatic vessels and it leaves the lymph node through an efferent lymphatic vessel as shown in Figure 1. There are estimated to be 400 to 600 lymph nodes in the human body. One of the major functions of the lymph nodes is to help defend the body against diseases by filtering bacteria and viruses from the lymph fluid, and to support the activities of the lymphocytes, which furnish resistance to specific disease causing agents. However, in abnormal conditions, as in the case of cancer and some infections, it is well known that lymph nodes can, act as holding reservoirs from where tumor cells, bacteria either or viruses can spread into other organs and regions of the body (5,7). For example, in the case of cancer, disseminating tumor cells can take root in lymph nodes and form residual metastatic tumors that are difficult to detect and treat.

Considering the importance of the lymphatics in relationship to many disease processes, the number of studies investigating drug delivery or targeting of other therapeutic agents to the lymphatics has been relatively modest (9). This chapter will focus on a review of the literature relevant to the delivery of liposomes to lymph nodes following SC injection.

Lymph Node Efferent

Figure 1 This diagram illustrates the structure of the lymph node. Efferent lymphatic vessels deliver lymph fluid to the lymph node and afferent lymphatic vessels take the lymphatic fluid from the lymph node. Each lymph node is supplied the fluid by an artery and a vein. Lymphatic fluid is filtered through the sinuses of the lymph nodes that are lined with macrophages to phagocytize foreign particulate agents. Lymph nodes also contain cortical, paracortical, and medullary regions that contain different immune cells.

Figure 1 This diagram illustrates the structure of the lymph node. Efferent lymphatic vessels deliver lymph fluid to the lymph node and afferent lymphatic vessels take the lymphatic fluid from the lymph node. Each lymph node is supplied the fluid by an artery and a vein. Lymphatic fluid is filtered through the sinuses of the lymph nodes that are lined with macrophages to phagocytize foreign particulate agents. Lymph nodes also contain cortical, paracortical, and medullary regions that contain different immune cells.

Lymph-node delivery of liposomes following injection into body cavities will be addressed in Chapter 15 of Volume III in this book.

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