Water-soluble polyphosphazenes

Polyphosphazenes can be considered as biomaterials in several different ways, depending on the type of utilization one can predict for these substrates. In this regard, we will consider three different topics concerning water-soluble POPs and their hydrogels, bioerodible POPs for drug delivery systems and for tissue engineering, and the surface implications of POP films. 

As already reported in Table 6, the solubility of phosphazene polymers is strongly influenced by the nature of the substituent groups attached at the phosphorus atoms along the -P=N- skeleton. Water-solubility, for instance, can be induced in polyphosphazenes by using strongly polar substituents (e.g. methylamine [84], glucosyl [495], glyceryl [496], polyoxyethylene mono-methylether [273] or sulfonic acid [497,498] derivatives), or may be promoted by acids or bases when basic (amino substituents like ethylamine [499]) or acid (e.g. aryloxy carboxylate [499] or aryloxy hydroxylate [295]) substituents are exploited. 

A number of polyphosphazenes are soluble in water. Examples include polymers with methylamino (39), glucosyl (36), glyceryl (35), or alkyl ether side groups (20). Here, we will consider one example, a polymer that is also well suited to the "clean" method of radiation crossUnking. 

We have already seen how water solubility and hydrolytic degradability can be built into the carrier macromolecule by the use of specific side groups. Here we will review an additional way in which drug molecules have been Linked to polyphosphazenes—by coordination. 

At another level, water-soluble polyphosphazenes are of interest as plasma extenders. In addition, specific polymers with pendent imidazolyl units have been studied as carrier macromolecules for heme and other iron porphyrins (structures and (44,45). (In structures M and the ellipse and Fe symbol represent heme, hemin, or a synthetic heme analog.)... 

Finally, a new water-soluble polyphosphazene was recently synthesized that has the structure shown in 36 (46). This polymer has two attributes as a biomedical macromolecule. First, the pendent carboxylic acid groups are potential sites for condensation reactions with amines, alcohols, phenols, or other carboxylic acid units to generate amide, ester, or anhydride links to polypeptides or bioactive small molecules. Second, polymer forms ionic crosslinks when brought into contact with di- or trivalent cations such as Ca or Ai3+. The crosslinking process converts the water-soluble polymer to a hydrogel, a process that can be reversed when the system... 

The versatility of water-soluble polyphosphazenes is in the variations in the structures that can be prepared. Structures with a low glass-transition temperature backbone can be modified with a variety of versatile side units. 

The versatility of water-soluble polyphosphazenes is in the variations in the structures that can be prepared. Structures with a low glass-transition temperature backbone can be modified with a variety of versatile side units. These may find use in solid polymeric ionic conductors, as a means to entrap and immobilize enzymes with retention of enzymic activity, and in biological functions as hydrogels with the capability of exhibiting biocompatibility and... 

In addition to providing fully alkyl/aryl-substituted polyphosphazenes, the versatility of the process in Figure 2 has allowed the preparation of various functionalized polymers and copolymers. Thus the monomer (10) can be derivatized via deprotonation—substitution, when aP-methyl (or P—CH2—) group is present, to provide new phosphoranimines some of which, in turn, serve as precursors to new polymers (64). In the same vein, polymers containing a P—CH3 group, for example, poly(methylphenylphosphazene), can also be derivatized by deprotonation—substitution reactions without chain scission. This has produced a number of functionalized polymers (64,71—73), including water-soluble carboxylate salts (11), as well as graft copolymers with styrene (74) and with dimethyl siloxane (12) (75). 

Examples of known phosphazene polymer blends are those in which phosphazenes with methylamino, trifluoroethoxy, phenoxy, or oligo-ethyleneoxy side groups form blends with poly(vinyl chloride), polystyrene, poly(methyl methacrylate), or polyethylene oxide).97 100 IPNs have been produced from [NP(OCH2CH2OCH2CH2OCH3)2] (MEEP) and poly(methyl methacrylate).101-103 In addition, a special type of IPN has been reported in which a water-soluble polyphosphazene such as MEEP forms an IPN with a silicate or titanate network generated by hydrolysis of tetraethoxysilane or tetraalkoxytitanane.104 These materials are polyphosphazene/ceramic composites, which have been described as suitable materials for the preparation of antistatic layers in the manufacture of photographic film. 

In a related development, the water-soluble polyphosphazenes, [NP(OCH2CH2NMe2)2] and [NP(NHCH2CH2NMe2)2] form 80 nm particles (polyplexes) when complexed to plasmid DNA. These particles may be used for gene delivery experiments.236... 

Bioactive units can be attached to a polyphosphazene chain by coordination or by covalent linkage. These two methods are considered separately. An attempt has been made to utilize a prototype, water-soluble polyphosphazene as a carrier for Pt antitumor agents . Such species are synthesized by the interaction of [NP(NHCH3)2] with K2[PtCl4] in CHCI3 in the presence of 18-crown-6 ether. 

This basic structure provides for considerable flexibility in the design of biomaterials, as described in a recent review [27]. By selection of the side groups on the polymer chain, both hydrophobic and hydrophilic polymers can be produced. Hydrophobic polyphosphazenes may be useful as the basis of implantable biomaterials, such as heart valves. The hydrophilic polymers can be used to produce materials with a hydrophilic surface or, when the polymer is so hydrophilic that it dissolves in water, cross-linked to produce hydrogels or solid implants. In addition, a variety of bioactive compounds can be linked to polyphosphazene molecules allowing the creation of bioactive water-soluble macromolecules or polymer surfaces with biological activity. 

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