Soluble-carrier systems

The choice of a macromolecular carrier depends on the intended clinical objectives and the nature of the therapeutic agents being used. In general, the properties of an ideal soluble carrier system include the following... 

A number of soluble carrier systems are described in detail below. 

Kempen et al. [176] synthesized a water-soluble cho-lesteryl-containing trigalactoside, Tris-Gal-Chol (I), which when incorporated in lipoproteins allows the utilization of active receptors for galactose-terminated macromolecules as a trigger for the uptake of lipoproteins. The effect of increasing concentrations of Tris-Gal-Chol on the removal of LDL and HDL from serum and their quantitative recovery in the liver is shown in Fig. 13. These data show that lipoproteins containing Tris-Gal-Chol can be used as a liver-specific drug-carrier system. 

Wu GY, Wu CH (1987) Receptor-mediated in vitro gene transformation by a soluble DNA carrier system. J Biol Chem 262 4429 1432... 

Soluble synthetic polymers have been widely employed as versatile drug carrier systems. Polymer chemistry allows the development of tailor made conjugates in which target moi-... 

Microspheres and nanoparticles often consist of biocompatible polymers and belong either to the soluble or the particle type carriers. Besides the aforementioned HPMA polymeric backbone, carriers have also been prepared using dextrans, ficoll, sepharose or poly-L-lysine as the main carrier body. More recently alginate nanoparticles have been described for the targeting of antisense oligonucleotides [28]. As with other polymeric carrier systems, the backbone can be modified with e.g. sugar molecules or antibody fragments to introduce cellular specificity. 

The formula of a liquid flavouring usually comprises the list of ingredients and a short summary of the corresponding blending instructions. At this stage the solubility of the ingredients in the carrier system is of high importance. Additional criteria can be summarised under the headline of shelf-life stability. 

In general, the specific constituents of milk are synthesized from small molecules absorbed from the blood. These precursors are absorbed across the basal membrane but very little is known about the mechanism by which they are transported across the membrane. Since the membrane is rich in lipids, and precursors are mostly polar with poor solubility in lipid, it is unlikely that the precursors enter the cell by simple diffusion. It is likely, in common with other tissues, that there are specialized carrier systems to transport small molecules across the membrane such carriers are probably proteins. 

The processes for the digestion and absorption of fat- and water-soluble vitamins are different, due to their solubility properties. Fat-soluble vitamins and their precursors (A, [1-carotene, D, E and K) are digested and absorbed by processes similar to those for dietary fats, mainly in the small intestine. Most water-soluble vitamins require specific enzymes for their conversion from natural forms in feed-stuffs into the forms that are ultimately absorbed. Unlike fat-soluble vitamins that are absorbed mostly by passive diffusion, absorption of water-soluble vitamins involves active carrier systems to allow absorption into the portal blood. 

In mitochondria there are two types of mechanisms for coupling the electron transport to the movement of protons across the membrane. The first is based on anisotropic reduction and oxidation of a lipid-soluble quinone inside the membrane. The quinone, coenzyme Q, becomes protonated upon reduction and diffuses to an oxidation site on the other side of the membrane where removal of electrons leads to proton release. This is essentially a proton carrier system with the hydroquinone acting as the proton carrier in the lipid phase of the membrane. A further refinement of this system in mitochondria provides for a coenzyme Q redox cycle where the movement of one electron through the chain allows for two protons to cross the... 

The carrier system, which can be either soluble or partaculate To effect a favorable distribution of the drug To protect the drug from metabolism To protect the drug from early clearance... 

This classification is sometimes rather arbitrary, as some soluble carriers are large enough to enter the colloidal size range. Another useful distinction is that with macromolecular carrier systems the drag is covalently attached to the carrier and has to be released through a chemical reaction. In contrast, with colloidal carriers, the drag is generally physically associated and does not need a chemical reaction to be... 

A crucial feature of such carrier systems is their solubility, which enables them to be taken up into target cells by the process of pinocytosis (which has been described in Section 1.3.3.2). The intact carrier enters... 

Poly(N-(2-hydroxypropyl)methaciylamide) (pHPMA) has been investigated as a soluble macromolecular carrier system, using doxorubicin as the active drag (Figure 5.5). 

Seymour, L.W. (1992) Passive Tumor Targeting of Soluble Macromolecules and Dmg Conjugates. Critical Reviews in Therapeutic Drug Carrier Systems, 9 135-187. 

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