Lipophilic agents

The production of CLS by the melt dispersion technique is based on the melting of the lipid core material together with the lipophilic agent (i.e., phospholipids). Afterward, a warm aqueous solution is added to the molten material and is mixed by various methods (i.e., mechanical stirring, shaking, sonication, homogenization). Then the preparation is rapidly cooled until lipid solidification and the formation of particle dispersion. This method was used by Olbrich et al. [19] to produce the cationic solid lipid nanoparticles to use as novel transfection agent. 

The thesis that all lipid-soluble compounds basically penetrate faster than water-soluble ones cannot be supported in this absolute form. A lipophilic agent can penetrate faster or slower or at the same rate as a hydrophilic agent, depending on the vehicle used. 

Somewhat surprisingly, microdialysis has also revealed that the time to maximum concentration (T ax) within the CNS is close to the Tj ax value in blood or plasma, irrespective of lipophilicity. For example, the CNS Tj ax for atenolol (log D7 4 = - 1.8) occurs at 2 min in the rat after intravenous administration [8]. In addition the rate of elimination (half-life) of atenolol and other polar agents from the CNS is similar to that in plasma or blood. The implication of these data is that poorly permeable drugs do not take longer to reach equilibrium with CNS tissue than more lipophilic agents... 

More recent in vitro studies have supported the original conclusions of Smith et al. (1919) in that HD forms a considerable and persistent reservoir within the epidermal layers of human skin (Chilcott et al., 2000) and it is also likely that other lipophilic agents, such as VX, may have similar skin absorption characteristics (Chilcott et al., 2005b). Clearly, the potential formation of a cutaneous reservoir of agent has important implications for the medical management of... 

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