Lymphatic transport, importance

Log P is not the only parameter to determine the ability of a molecule to be transported via the lymph. As the lymphatic absorption is associated with chylomicron formation, which is composed mainly from a triglycerides core (85%-92%) [62], the solubility of the prodrug in triglycerides is an important indicator for lymphatic transport capacity potential. Charman and Stella suggested that solubility in triglycerides of at least 50 mg/mL is required before lymphatic transport is likely to occur [63],... 

The consequences of intestinal lymphatic transport are therefore more wide ranging than the opportunity to target the intestinal and central lymph and to avoid first-pass metabolism. Indeed, drug transport by means of the intestinal lymph may markedly alter the patterns of subsequent systemic drug clearance and disposition, and these profound alterations could be stimulated simply by a change in formulation. Importantly, the common approach of the use of plasma AUC as an indicator of the available fraction may be misplaced when dealing with lipophilic and lymphotropic drug molecules. 

Most polyanions are water soluble, which is essential for biological transport and more importantly for systemic administration, since injection of suspensions into blood system can cause "colloido-clasmic shock" or "macromolecular syndrome" with major hypersensitive clinical toxicity. Water-soluble polyanlonlc polymers can be distributed in a living system by means of blood or lymphatic circulation, by cellular transport through the involvement of mobile phagocytic cells, and absoirption on cell surfaces. 

An additional route of uptake upon peroral administration is the passage of the M-cells of the Peyer s patches [18]. Although this route in essence has only a low transport capacity, it is of importance for mucosal (peroral) vaccination, for example. The Peyer s patches are located in the small intestine where M-cells, which neither possess a mucus nor a glycocalix layer in comparison to the adjacent enterocytes, allow the drug uptake via transcytosis. The drug is then transported into the lymphatic system and causes an immune response in the case of the vaccination approach. Absorption via M-cells in essence is possible due to the decreased enzymatic activity and their rather high permeability. 

The majority of the fluid that is filtered from the microcirculation into the interstitial space is carried out of the tissue via the lymphatic network. This unidirectional transport system originates with a set of blind channels in distal regions of the microcirculation. It carries a variety of interstitial molecules, proteins, metabolites, colloids, and even cells along channels deeply embedded in the tissue parenchyma toward a set of sequential lymph nodes and eventually back into the venous system via the right and left thoracic ducts. The lymphatics are the pathways for immune surveillance by the lymphocytes and thus, they are one of the important pathways of the immune system [Wei et al, 2003]. 

The oil represents one of the most important components in the formulation of the microemulsion. It can solubilize the required dose of the lipophilic drug and can also increase the fraction of lipophilic drug transported via the intestinal lymphatic system, thereby increasing absorption from the GI tract, depending on the molecular nature of the triglyceride. ... 

Microemulsions are transparent systems of two immiscible fluids, stabilized by an interfacial film of surfactant or a mixture of surfactants, frequently in combination with a cosurfactant. These systems could be classified as water-in-oil, bicontinuous, or oil-in-water type depending on their microstructure, which is influenced by their physicochemical properties and the extent of their ingredients. - SMEDDSs form transparent microemulsions with a droplet size of less than 50 nm. Oil is the most important excipient in SMEDDSs because it can facilitate self-emulsification and increase the fraction of lipophilic drug transported through the intestinal lymphatic system, thereby increasing absorption from the gastrointestinal tract. Long-chain and medium-chain... 

Blood and lymphatic vessels are soft tissues with densities which exhibit nonlinear stress-strain relationships [1]. The walls of blood and lymphatic vessels show not only elastic [2, 3] or pseudoelastic [4] behavior, but also possess distinctive inelastic character [5, 6] as well, including viscosity, creep, stress relaxation and pressure-diameter hysteresis. The mechanical properties of these vessels depend largely on the constituents of their walls, especially the collagen, elastin, and vascular smooth muscle content. In general, the walls of blood and lymphatic vessels are anisotropic. Moreover, their properties are affected by age and disease state. This section presents the data concerning the characteristic dimensions of arterial tree and venous system the constituents and mechanical properties of the vessel walls. Water permeability or hydraulic conductivity of blood vessel walls have been also included, because this transport property of blood vessel wall is believed to be important both in nourishing the vessel walls and in affecting development of atherosclerosis [7-9]. 

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