Lymphatic system particulates

Factors known to influence the clearance of drugs from interstitial sites, following extravasation or parenteral interstitial or transepithelial administration, include size and surface characteristics of particles, formulation medium, the composition and pH of the interstitial fluid, and disease within the interstitium. Studies indicate that soluble macromolecules smaller than 30 nm can enter the lymphatic system, whereas particulate materials larger than 50 nm are retained in the interstitial sites and serve as a sustained-release depot. The use of lipids or an oil in a formulation and the presence of a negative surface charge all appear to... 

Particulates can either cross into the lymphatics at the spaces in the tracheobronchial wall where epithelial cells directly overlay lymphoid tissue or pass through the endothelium of thin capillary walls in the air spaces. The transfer is a portion of a clearance mechanism that assists the lung in maintaining its normal function of gas exchange. Absorbtion and transport mechanisms of a variety of materials that enter the lymphatics continue to be studied. It was shown early in this century that water, dyes, proteins, bacteria, lipids, and particulates enter the lymphatic system relatively easily. The rates of transport and quantity vary with the size and chemistry of the material. Classic studies by Kihara (1924 1950) and Nishikawa (1941) dem-... 

The route of antigen administration depends on the nature of the antigen itself, the animal species, the use of an adjuvant, and the immunological response. When producing antisera from rabbits, subcutaneous and intradermal administration are the most popular routes. Intramuscular injections can be used in the presence of Freund adjuvants because this route provides rapid access to the lymphatic system. The intravenous route is used with particulate antigens because injection can produce a response, which, although rapid, is not sustained. 

The two primary functions of the lymphatic system are filtering of particulate matter before it enters the vascular system and development and delivery of components to combat foreign substances. It is selective for particulate size and returns the nearly 200 grams of protein that leak out through capillary filtration every 24 hours. 

Figure 6.15 Schematic diagram of a portion of the epithelium covering above a lymphatic nodule in a Peyer s patch (mouse). Attenuated M cells (M) extend as membranelike cytoplasmic bridges between the absorptive columnar epithelial cells present on either side (C). Beneath the M cell lies a small nest of intraepithelial lymphocytes (L) together with a central macrophage (Mac). The M cell provides a thin membrane-like barrier between the lumen above and the lymphocytes in the intercellular space below. This M cell has taken up the macromolecules and particulate matter that reach it and macrophages (Mac) may ingest them. Modified from D.H. Cormack. Lymphatic tissue and the immune system. D.H.Cormack (ed.) (1987) Ham s Histology, J.B. Lippincott Company, Philadelphia, pp. 234-263...

Lymph nodes vary in size and are aggregates of lymphatic tissue. Kidney bean-shaped, each consists of a cortex containing germinal centers and an inner medulla. Reticuloendothelial ceils are located along trabecular connective tissue and act as a filtration system for particulate matter. An efferent lymph vessel exits at the hilum, along with a vein, and is accompanied by an artery. An afferent lymph vessel enters on the convex side through the capsule. 

As particulate matters and synthetic nanomaterials are deposited in the respiratory system, they are further translocated to other organs via several pathways. The first step for the translocation is endocytosis or transcytosis [35], after which particulate matters and nanomaterials will be further transported to other organs via the blood, lymphatic drainage or, in very rare cases, the sensory nervous system [86]. The particle size, shape and surface properties greatly affect these processes. 

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