Polyanionic polymers

Hydrophobization of Polyanionic Polymers to Achieve Higher Biological Activity... 

Since the pioneer work by Merigan in 1967 [1], many kinds of synthetic or natural polyanionic polymers have been examined for their biological activities [2-8], such as cytotoxicity, antiviral activity, antitumor activity, and immunomodulating activity. Although the biological results were interesting, the extent of activity for clinical application was still low. 

Several mechanisms between drug-encapsulated liposomes and cells was presented [9,10]. Sunamoto and coworkers [11] applied the liposomal technique for improving the biological activity of polyanionic polymers. 

We modified polyanionic polymers by use of a grafting reaction of hydrophobic groups onto the polymers. After an extensive evaluation for the affinity of the hy-drophobically modified (hydrophobized) polymers to cell membrane, the immuno-stimulating activity of polymers was investigated by in vitro or ex vivo experiments. Consequently, the increased biological activity was found in the hydrophobized polymer, indicating that... 

Based on the data in Figs. 2 and 4, it appears that the affinity of the polyanionic polymer for cell membrane can be increased by the hydrophobization of polymers. 

Figure 3 The principle for the evaluation of the interaction between modified or unmodified polyanionic polymer and liposomal membrane.

There was no distinct difference between polymers having different molecular weights. From the data in Figures 2, 4, 5, and 6, it seems to be established that the affinity of polyanionic polymers for cell membrane is adjustable by a simple grafting of hydrophobic groups. 

Based on these observations in Figs. 8 and 9, it is suggested that the hydrophobic group modification (hy-drophobization) is an effective method for improving the immuno-stimulating activity of polyanionic polymers. 

Some microbial exopolysaccharides contain the inorganic substituents phosphate and sulphate. Phosphate has been found in exopolysaccharide from bacteria of medical importance, including Escherichia coli. Sulphate is far less common than phosphate and has only been found in spedes of cyanobaderia. In addition to these inorganic components, which form part of the structure of some exopolysaccharides, all polyanionic polymers will bind a mixture of cations. Exopolysaccharides are, therefore, purified in the salt form. The strength of binding of the various cations depend on the exopolysaccharide some bind the divalent cations calrium, barium and strontium very strongly, whereas others prefer certain monovalent cations, eg Na ... 

Polyanionic polymers can enter into biological functions by distribution throughout the host and they behave similar to proteins, glycoproteins and polynucleotides which modulate a number of biological responses related to the host defense mechanism. These are enhanced immune responses, and activation of the reticuloendothelial system (RES) macrophages. 

Presently there are two polyanionic polymers, MVE-2 and Carbetimer, that have undergone considerable clinical evaluation as antitumor agents. 

Poly(starch-g-((l-amidoethylene)-co-(sodium 1-carboxylatoethylene))). Poly(l-amidoethylene) is, however, rarely used as a viscosifier. Instead, the homopolyraer is reacted with base (hydrolyzed with NaOH) to convert some of the amide units of the polymer to carboxylic acid units. The acid units on the hydrolyzed polymer dissociate in water and produce a polyanionic polymer. This polyelectrolyte expands in water because of ion-ion repulsion and, as an enlarged molecule, is a better viscosifier. 

Together with the primary secretory products (enzymes, hormones, neurotransmitters, etc.) secretory granules contain a pair of countercharged chemical moieties a polyanionic polymer matrix, and a cation or polycation. These countercharged pairs, which are found ubiquitously inside different types of secretory granules, gave us the first clue that a polymer gel phase transition -... 

Nucleic Acid Analogs and Polyanionic Polymers as Polymer Drug - 127... 

The antitumor activity of synthetic 5-FU derivatives, polymeric prodrugs having 5-FU unit, and physically 5-FU incorporated polymers has been investigated [44-55], Moreover recent attention has been focused on syntetic polyanionic polymers [41], and drug-polyanion conjugates have been prepared to evaluate the activities [56],... 

Consequently, both nucleic acid analogs such as poly(VAd) and pharmaceutically active syntetic polyanionic polymers having hydrophobic moieties may interact with nucleic acids in vivo. 

Shown in Fig. 19 are the results of CF-release induced by poly(VAd-co-MAn) at 37 °C and 50 °C, respectively. At 50 °C, CF was released by the addition of the copolymer, particularly for the high molecular weight polymers. At 37 °C, it is less serious compared with previous results observed for polyanionic polymers [69]. 

The mechanism of macrophage activation with polymer drugs such as synthetic polynucleotides and polyanionic polymers is not clearly understood. Two possibilities based on physiological responses are (1) the direct interaction or perturbation by the polymer drug with the cell cytoplasma membrane, and (2)... 

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