Lymphatic clearance

A six compartments model representing the pharmacokinetics of dust movement within the alveolar area of the lungs and lymph nodes was proposed by Smith (1985) including free particles and two macrophage departments on the alveolar surfaces, temporary and encapsulation particles in the interstitial area, and particles in lymph nodes. Seven processes control the quantities of particles in each of the three areas  

Removal of dust laden macrophages from the lungs  

Penetration of free particles through the alveolar membrane into the cells and interstitial area  

Sequestration of free particles or particles in macrophages in the interstitial area by fibrosis or other processes  

Transportation of free or phagocytosed interstitial particles to the lymph nodes and 

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Clearance of endogenous and exogenous immunoglobulin takes place via a number of mechanisms. Among these are phagocytosis by mononuclear phagocytic cells (reticuloendothelial clearance), lymphatic clearance, and other tissue-specific and/or specialized mechanisms (discussed in more detail below). 

Figure 5.23 Clearance versus filtration rate for simple homogeneous transport through a tissue barrier. Redrawn from [23]. The solid lines indicate clearance for different values of the PS product. The dashed lines indicate transport in the absence of diffusion Pe 1). Equation 5-34 is plotted for cr, = 0.9 at steady state (i.e., lymphatic clearance is equal to solute flux, see [23]).

Defective lymphatic clearance of macromolecules and lipids from interstitial tissue (prolonged retention of these substances)... 

Fig. 3 Structures of (a) normal and (b) tumor tissue, and the in/out transport from capillaries of various substances. Although large macromolecules cannot penetrate normal tissue, and small molecules and proteins are cleared by lymphatics, blood vessels in tumors present large fenestrations that cause macromolecules to permeate extensively into the tumor tissue. Moreover, slow venous return and poor lymphatic clearance retain macromolecules in the tumor. These phenomena are called the enhanced permeability and retention (EPR) effect [18]. Reprinted with permission from Reference [18]...

Static barriers (different layers of cornea, sclera, and retina, including blood aqueous and blood-retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in dosage form, especially to the posterior segment. 

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