Lipophilic drugs incorporated

Preparation ofAmphiphilic/Lipophilic Drug Incorporating or Encapsulating DRVs (as reported tor PRE In (15))... 

Figure 22.1 A. Schema for a physiologically based pharmacokinetic model incorporating absorption in the stomach and intestines and distribntion to various tissues. B. Each organ or tissue type includes representation of perfusion (Q) and drug concentrations entering and leaving the tissue. Fluxes are computed by the product of an appropriate rate law, and permeable surface area accounts for the affinity (e.g., lipophilic drugs absorbing more readily into adipose tissue). Clearance is computed for each tissue based on physiology and is often assumed to be zero for tissues other than the gut, the liver, and the kidneys.

Kaneko et al. (1993) have described a group of lipophilic ascorbic-acid analogues that have been studied in cultured human umbilical vein endothelial cells that were first incubated with test drug and then exposed to lipid hydroperoxides. Although ascorbate itself did not protect the endothelial cells, derivatives like CV3611 protected. Pretreatment was necessary. CV3611 was synergistic with vitamin E. The authors concluded that these lipophilic antioxidants incorporate into endothelial cell membranes where they are effective inhibitors of lipid peroxidation. In contrast, lipophobic antioxidants were not effective in their hands (Kaneko et al., 1993). 

Liposomes are useful as carrier systems for therapeutic or diagnostic drugs. Depending on the chemical structure of the loaded compound, it can either be incorporated into the membrane layer as is observed for lipophilic drugs or stored in the aqueous compartment at the centre of the vesicle (hydrophilic substances). 

Any conclusions about the organization of different components within the dispersions should take the ultrastructure of the systems into consideration. The surface-active agents that act as stabilizers for the nanoparticles are often able to form additional colloidal structures, such as vesicles or micelles, by self assembly. In addition to a potential importance in the formation and stability of the dispersions, such structures contain lipophilic domains that may represent alternative compartments for the localization of incorporated drugs. As a consequence, their presence may affect drug incorporation and release. 

Figure 10.6 The antitumoral camptothecin (CPT), a lipophilic drug extracted from the Chinese tree Camptotheca acuminata, can be incorporated into the liposome bilayer due to its lipophilic character. The CPT-containing liposomes are studied as antitumor drug formulations. (Modified from Stano et al 2004.)...

The presence of lipids in the GI tract stimulates gall bladder contracts and biliary and pancreatic secretions, including bile salts, phospholipids, and cholesterol. These products, along with the gastric shear movement, form a crude emulsion, which promotes the solubilization of the coadministered lipophilic drug. Exogenous surface-active agents incorporated into the formulation may further stimulate the solubilization of the lipophilic compound. 

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