Lipophiles and Hydrophiles

In 2003, Zeliger reported that in all cases of these unusual effects of mixtures cited in the literature, the mixtures contained at least one lipophilic and one hydrophilic chemical. A lipophilic chemical is one that exhibits preferential solubility in relatively less polar species. A hydrophilic chemical is one that exhibits preferential solubility in relatively more polar species. Lipophiles promote the permeation of hydrophiles through mucous membranes resulting in the absorption of greater quantities of hydrophilic species than would be absorbed if the lipophile were not present. Once absorbed, the mixtures of chemicals may affect the body in ways not anticipated from the actions of single chemicals alone. It was found that the effects of the absorbed mixtures may be acute or chronic.  

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Lanolin alcohols are obtained by saponification of purified wool grease, a mixture of high molecular esters that is recovered in wool (qv) scouring. Ethoxylation of purified lanolin alcohols yields a full series of lipophilic and hydrophilic nonionic emulsifiers whose largest use is in cosmetic preparations. Manufacturers include Amerchol, Croda, ICI, Henkel Corporation, Westbrook Lanolin, Witco, and Pulcra, SA. 

An important factor in determining the course of uptake, transport, and distribution of xenobiotics is their polarity. Compounds of low polarity tend to be lipophilic and of low water solubility. Compounds of high polarity tend to be hydrophilic and of low fat solubility. The balance between the lipophilicity and hydrophilicity of any compound is indicated by its octanol-water partition coefficient (K J, a value determined when equilibrium is reached between the two adjoining phases ... 

In 2003, Prior and others described methods for the extraction and analysis of hydrophilic and lipophilic antioxidants, using modifications of the ORAC procedure. These methods provide, for the first time, the ability to obtain a measure of total antioxidant capacity in the protein free plasma, using the same peroxyl radical generator for both lipophilic and hydrophilic antioxidants. This assay was also used to measure the total antioxidant capacity of guava fruit extracts (Thaipong and others 2006). 

Wu X, Beecher GR, Holden JM, Haytowitz DB, Gebhardt SE and Prior RL. 2004. Lipophilic and hydrophilic antioxidant capacities of common foods in the United States. J Agric Food Chem 52(12) 4026-4037. 

Grissom, R.E., Jr. C. Brownie, and F.E. Guthrie. 1987. In vivo and in vitro dermal penetration of lipophilic and hydrophilic pesticides in mice. Bull. Environ. Contam. Toxicol. 38 917-924. 

Theory and computational aspects of intestinal permeability have been reviewed in detail by Egan and Lauri [27], Briefly, a drug must be somewhat permeable through the membrane of the intestinal tract if it is to be administered orally and achieve systemic exposure. The rate of membrane permeability is strongly related to the lipophilicity and hydrophilicity of the molecule. Thus, models with a small number of descriptors related to those two properties can provide useful predictions of drug absorption. 

Tukker JJ and Poelma FG (1988b) Site-Dependent Absorption in the Intestine of the Rat—Variation in Absorption Between Lipophilic and Hydrophilic Compounds. Pharmac Weekblad-Sci Ed 10 pp 183. 

Initial screening of lipophilic and hydrophilic extracts against influenza A/WY/03/2003 (H3N2) was selected from a library of diverse marine invertebrates, algae, and microorganisms. The primary influenza screen used in this study begins with a microscopic evaluation of the cytopathic effect of extracts on virus-infected mammalian cells and is quantified by an MTT stain. From 800 screened extracts, only one, well A4 in Fig. 1.1, which is the crude extract from G. 

Other aspects of solvation have included the use of surfactants (SDS, CTAB, Triton X-100), sometimes in pyridine-containing solution, to solubilize and de-aggregate hemes, i.e., to dissolve them in water (see porphyrin complexes, Section 5.4.3.7.2). An example is provided by the solubilization of an iron-copper diporphyrin to permit a study of its reactions with dioxygen and with carbon monoxide in an aqueous environment. Iron complexes have provided the lipophilic and hydrophilic components in the bifunctional phase transfer catalysts [Fe(diimine)2Cl2]Cl and [EtsBzNJpeCU], respectively. 

In summary, the lipophilic and hydrophilic ORACpp values for more than 100 common foods in U.S. markets are obtained for the first time. 

These drugs are of similar structure and size (mol. wt. 220-329) and are simultaneously lipophilic and hydrophilic—properties which are essential to their mode of action. With the exception of cocaine, all local anaesthetics in clinical use are synthetic compounds. 

For most purposes, it is convenient to classify suppository bases according to their physical characteristics into two main categories and a third miscellaneous group (i) fatty or oleaginous bases (ii) water-soluble or water-miscible bases, and (iii) miscellaneous bases, general combinations of lipophilic and hydrophilic substances (43). Appendix V presents a survey of commercial pharmaceutical suppositories and the respective suppository bases. 

Figure 3.10—Formation of bonded organosilanes at the interface of silica gel. Representation of organic monomers and polymers at the surface of silica gel. The arrangement Si-O-Si C is more stable than Si O C. This reaction leads to a carbon content of 4 or 5%. Other reactions can also be used (hydrosilylation in particular). When a monolayer of hydrocarbons is bonded to the surface of silica, they orient in a particular manner at the interface due to their lipophilic and hydrophilic character.

Lipid-based formulations offer a large variety of optional systems. They can be made as solutions, suspensions, emulsions, self-emulsifying systems and microemulsions. Moreover, it is possible to form blends that are composed of several excipients they can be pure triglyceride (TG) oils or blends of different TG, diglyceride (DG) and monoglyceride (MG). In addition, different types of surfactants (lipophilic and hydrophilic) can be added, as well as hydrophilic co-solvents. Lack of enhanced absorption when one of the above key formulations is tested does not necessarily indicate the effectiveness of alternative lipid-based formulations, and their suitability has to be examined. 

Extensive investigations on the accelerant activities of DMSO show it to be effective in promoting the flux of both lipophilic and hydrophilic permeants, e.g., antiviral agents,... 

Lee, W.R., et al. 2001. Transdermal dmg delivery enhanced and controlled by erbium YAG laser A comparative study of lipophilic and hydrophilic drugs. J Control Release 75 155. 

Action on the membrane components Numerous studies have shown that the passive transcellular transport of hydrophilic compounds, including macromolecules such as peptides, can be enhanced by interaction of the penetration enhancers with both the phospholipid bilayer and the integrated proteins, thereby making the membrane more fluid and thus more permeable to both lipophilic and hydrophilic compounds. 

FIGURE 12-1 Structure of lidocaine. The basic structure of a lipophilic and hydrophilic group connected by an intermediate chain is common to most local anesthetics. 

Extracts of the kava root contain both lipophilic and hydrophilic components. The active constituents of kava are referred to as kavalactones or kavapyrones. The active enolides and dienolides are thought to be kawain (kavain), methysticin, and yangonin. 

Figure 11 Proposed reaction mechanism for TNP hydrolysis catalyzed by lipophilic and hydrophilic zinc(II)-cyclen complexes, lib and 2b.

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