Large molecule compounds, membrane permeation

The encapsulation of drug molecules also leads to delivery systems, especially in the case of hydrophilic compounds where a permeation barrier with depot effect is provided. The permeation velocity is controlled by the properties of the membranes, as well as by the lipophilicity and size of the incorporated drug. Even large molecules are released slowly in the body, but unfortunately this also occurs under storage conditions. As liposomes do not have a solid surface, an equilibrium is built up between incorporated or adhered drug and free drug molecules, and this can lead to bursf effects when liposome dispersions are diluted. 

The rate and extent of intestinal permeation is dependent on the physicochemical properties of the compound (see Sections 16.1.2 and 16.4.3) and the physiological factors. Drugs are mainly absorbed in the small intestine due to its much larger surface area and less tight epithelium in comparison to the colon [17]. The permeation of the intestine may be affected by the presence of an aqueous boundary layer and mucus adjacent to cells, but for a majority of substances the epithelial barrier is the most important barrier to drug absorption. The lipoidal cell membrane restricts the permeability of hydrophilic and charged compounds, whereas large molecules are restricted by the ordered structure of the lipid bilayer. 

The Ro5 is useful where drugs are passively transported across membranes, since exceptions include antibiotics, antifungals, vitamins and cardiac glycosides, molecules that are known to make use of transporters for their permeation. However, there has been increased recent interest in the role of transporters, and it has been proposed that, given the large number of transporter systems, most, if not all, compounds may be transporter substrates. 

Another approach that has been proven to be successful is the incorporation of reactive moieties in polymers to selectively increase the affinity of one penetrant over the others, the so-called facilitated transport mechanisms. In this case a chemical contribution is added to the physical flux in view of a chemical reaction of the target penetrant with the reactive moieties present in the membrane matrix, whereas aU of the other components are able to permeate only because of the physical mechanism. This approach allows the simultaneous achievement of high flux for the target compound and large selectivity, moving perpendicularly to the membrane upper bound. A typical example is the use of amine-based polymers as a membrane matrix under humid conditions because water is needed to catalyze the chemical reaction [37,38]. The carrier can be chemically bonded to the membrane matrix [39] or low-molecular-weight molecules able to freely move in the swollen matrix [40]. Nevertheless, this approach has also been used for the recovery of pharmaceutical chemicals, such as Cephalexin [41], as well as metal ions from waste water [42]. 

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