Polyphosphazenes biomedical applications

Biomedical Applications. In the area of biomedical polymers and materials, two types of appHcations have been envisioned and explored. The first is the use of polyphosphazenes as bioinert materials for implantation in the body either as housing for medical devices or as stmctural materials for heart valves, artificial blood vessels, and catheters. A number of fluoroalkoxy-, aryloxy-, and arylamino-substituted polyphosphazenes have been tested by actual implantation ia rats and found to generate Httle tissue response (18). 

Figure 12.30 Potential uses of polyphosphazenes (a) A thin film of a poly(aminophosphazene) sueh materials are of interest for biomedical applications, (b) Fibres of poly[bis(trifluoroethoxy)phosphazene] these fibres are water-repellant, resistant to hydrolysis or strong sunlight, and do not burn, (c) Cotton cloth treated with a poly(fluoroalkoxyphosphazene) showing the water repellaney eonferred by the phosphazene. (d) Polyphosphazene elastomers are now being manufaetured for use in fuel lines, gaskets, O-rings, shock absorbers, and carburettor eomponents they are impervious to oils and fuels, do not bum, and remain flexible at very low temperatures. Photographs by eourtesy of H. R. Allcock (Pennsylvania State University) and the Firestone Tire and Rubber Company.

Applications. Polymers with small alkyl substituents, particularly (13), are ideal candidates for elastomer formulation because of quite low temperature flexibility, hydrolytic and chemical stability, and high temperature stability. The ability to readily incorporate other substituents (in addition to methyl), particularly vinyl groups, should provide for conventional cure sites. In light of the biocompatibility of polysiloxanes and P—O- and P—N-substituted polyphosphazenes, poly(alkyl/arylphosphazenes) are also likely to be biocompatible polymers. Therefore, biomedical applications can also be envisaged for (3). A third potential application is in the area of solid-state batteries. The first steps toward ionic conductivity have been observed with polymers (13) and (15) using lithium and silver salts (78). 

Secondary reactions of these types are widely used to produce polyphosphazenes that are required for biomedical applications or for polymer grafting reactions. They are also used to modify the surfaces of poly(organophosphazene), as discussed in the following section. 

Allcock and coworkers developed derivatives of the phosphazene polymers suitable for biomedical applications [35, 36]. Long-circulating in the blood, 100-120 nm in diameter, PEO-coated nanoparticles of the poly(organophospazenes) containing amino acids have been prepared. The PEO-polyphosphazene copolymer or poloxamine 908 (a tetrafunctional PEO copolymer) has been deposited on their surface [37]. 

Specialty polymers achieve very high performance and find limited but critical use in aerospace composites, in electronic industries, as membranes for gas and liquid separations, as fire-retardant textile fabrics for firefighters and race-car drivers, and for biomedical applications (as sutures and surgical implants). The most important class of specialty plastics is polyimides. Other specialty polymers include polyetherimide, poly(amide-imide), polybismaleimides, ionic polymers, polyphosphazenes, poly(aryl ether ketones), polyarylates and related aromatic polyesters, and ultrahigh-molecular-weight polyethylene (Fig. 14.9). 

J. Crommen, J. Vandorpe, E. Schacht, Degradable polyphosphazenes for biomedical applications, J. Control. Release 24 (1-3) (1993) 167-180. 

L.S. Nair, et al.. Fabrication and optimization of methylphenoxy substituted polyphosphazene nanofibers for biomedical applications. Biomacromolecules 5 (6) (2004) 2212-2220. 

M.T Conconi, et al., Electrospun polyphosphazene nanofibers for in vitro osteoblast culture, in A. Andrianov (Ed.), Polyphosphazenes for Biomedical Applications, Wiley-Intersdence, Hoboken, NJ, 2009. 

H.R. Allcock, Expanding options in polyphosphazene biomedical research, in Polyphosphazenes for Biomedical Applications, John Wiley Sons, Inc, New Jersey, 2008, pp. 15 3. 

Chapter 7 by Allcock and Pugh describes the family of polyphosphazene polymers that have a structure based on a backbone of alternating phosphorus and nitrogen atoms, and with two organic side groups attached to each phosphorus. The authors of this chapter show that polyphosphazenes are mostly synthesized by a macromolecular substitution method in which a reactive intermediate, polydichlorophosphazene, is used as a substrate for the replacement of the chlorine atoms by organic nucleophiles. The potential uses for these polymers are in the field of aerospace, fire resistant polymers, fuel cells, and also for biomedical applications. 

The biomedical applications of polyphosphazene derivatives and phos-phoiylated polymers will not be covered in this review, although... 

As already reflected by the number of review papers, the interest in biomedical applications of polyphosphazenes continues to grow. The biodegradable polymer NP(NHC6H4C02H-4)i.8(NHC6H4C02H-4)o.2 n has been prepared and fully characterized. The carboxylato groups can react with Ca -ions to form crosslinks and to convert the water-soluble polymer to a hydrogel. Controlled drug release experiments have been carried out for chitosan en-... 

Glucose-substituted polyphosphazenes such as (12.242b) also lead to water-soluble products with potential biomedical applications. The fact that aromatic azo groups can be successfully introduced into the polymer side chains as in (12.242a) suggests that such materials may prove to be the precursors of a new class of azo polymer dyestuffs (Section 12.8) [90,91]. 

Polyphosphazenes have already been investigated for biomedical applications, especially in controlling the release of chemotherapeutic agents (Cho and Allcock, 2007) (and thus in the drug delivery field) and in the temporary replacement of body parts (Deng et al., 2010). For example, following... 

A wide range of polyphosphazenes have been used for a number of biomedical applications. Examples are inert biomaterials for cardiovascular and dental uses, bioerodible and water soluble polymers for controlled drug delivery applications (Allcock et al, 1990). 

Another field of biomedical applications in which polyphosphazenes can be used, is the field of drug delivery systems. One can distinguish two types of drug delivery systems. In a first type of systems, the drug to be released, is covalently attached to the polymer backbone. In a second concept, the polymer material is used as matrix system in which the drug is physically dispersed. 

Biomedical Applications. Biomedical applications were investigated by a number of polyphosphazene research groups (181). The most important studies concerned biocompatibility, biodegradation, enz5une immobilization, and drug delivery (182,183). Polyphosphazene implants and prosthe-ses were also examined. Biocompatibility through appropriate manipulation of surface or bulk chemistry was studied extensively (184). Works on the synthesis and cross-linking of amphiphilic polyphosphazenes (94), heparin immobilization (185-187), and other surface functionalizations (4,101) were reported. 

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