Polyphosphazenes drug release from

Andrianov, A.K. and Payne, L.G. (1998). Protein release from polyphosphazene matrices. Adv. Drug Delivery Rev., 31, 185-196. 

Polyphosphazenes are a relatively new class of biodegradable polymers. Their hydrolytic stability or instability is determined not by changes in the backbone structure but by changes in the side groups attached to an unconventional macromolecular backbone. Synthetic flexibility and versatile adaptability of polyphosphazenes make them unique for drug delivery applications. For example, Veronese et al.18 prepared polyphos-phazene microspheres with phenylalanine ethyl ester as a phosphorous substituent and loaded it with succinylsulphathiazole or naproxen. The kinetics of release from these matrices were very convenient in yielding local concentrations of the two drugs that are useful per se or when mixed with hydroxyapatite for better bone formation. Polyphosphazene matrices are also considered as potential vehicles for the delivery of proteins and vaccines.19... 

Payne, L. G. and A. K. Andrianov, 1998, Protein release from polyphosphazene matrices. Adv Drug Deliv Rev 31 185-196. 

One more successful example is the preparation of covalently bound antibiotics onto various amino-acid-ester-substituted polyphosphazenes [99]. The amino acid ester groups could be used to fine-tune the rate of hydrol)n ic degradation and thus drug release, and the antibiotics ciprofloxacin and norfloxacin could be covalently attached to the polyphosphazene backbone via the piperazinyl groups. In aqueous media, the antibiotics released were measured to be between 4 and 30% over a 6-week period for films prepared from... 

Aside from the commercial fluoroelastomer mentioned above, many applications for polyphosphazenes have been proposed. In particular, recent smdies have looked at modified polyphosphazenes as potential biomedical materials [20,21]. Phosphazenes with hydrophilic side chains in water exhibit a lower critical solution temperature (LCST) (Section 3.3) and their hydrogels have been considered for controlled drug release and other biomedical applications [22-24]. However, no large-scale use has yet emerged. 

The biomedical uses of polyphosphazenes mentioned earlier involve chemistry that could in principle be carried out on a classical petrochemical-based polymer. However, in their bioerosion reactions, polyphosphazenes display a uniqueness that sets them apart. This uniqueness stems from the presence of the inorganic backbone, which in the presence of appropriate side groups is capable of undergoing facile hydrolysis to phosphate and ammonia. Phosphate can be metabolized, and ammonia is excreted. If the side groups released in this process are also metabolizable or excretable, the polymer can be eroded under hydrolytic conditions without the danger of a toxic response. Thus, poljnners of this tjT are candidates for use as erodible biostructural materials or sutures, or as matrices for the controlled delivery of drugs. Four examples will be given to illustrate the opportunities that exist. 

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