Drug delivery 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. 

A different approach to polyphosphazene-based drug delivery systems deals with hydrolytically unstable phosphazene substrates, able to degrade in a controlled way under physiological conditions in human body. A list of these bio-erodible substrates is reported in Table 21. 

These discoveries generated a lot of effort over the successive 25 years in the preparation of especially designed drug delivery systems for the controlled release of radioactive progesterone [654], colchicine [656], naproxen [657,673, 674], mitomycin C [675-677], inulin [678], trimethoprin [657], succinylsul-fathiazole [657], ethacrynic acid [653], and steroids [633], regardless of whether these drugs are physically trapped in polyphosphazene matrices, or chemically bonded to the polymer skeleton. 

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

The use of synthetic polymers in medicine and biotechnology is a subject of wide interest. Polymers are used in replacement blood vessels, heart valves, blood pumps, dialysis membranes, intraocular lenses, tissue regeneration platforms, surgical sutures, and in a variety of targeted, controlled drug delivery devices. Poly(organosiloxanes) have been used for many years as inert prostheses and heart valves. Biomedical materials based on polyphosphazenes are being considered for nearly all the uses mentioned above. 

A final biomedical use for polyphosphazenes is as components in microspheres, vesicles, and micelles for use in drug-delivery applications. Microspheres are pseudo-spherical constructs that range in size from 1 to 600 microns. Vesicles (lipozomes) are hollow, water-filled bilayer spheres with diameters that range from 0.03 tolO microns. Micelles typically have diameters near 1 micron (100 nanometers). Idealized representations of these three structures are shown in Figure 3.23, together with the location of trapped drug molecules. 

Liquid crystalline, ferroelectric, and photochromic systems Controlled drug-delivery from polyphosphazenes Use in bone tissue engineering... 

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... 

The biomedical use of polyphosphazenes for drug delivery and controlled release systems still draws considerable attention. It has been demonstrated for the degradable polymer [NP(NHCH2C02Et)2]n that the rate of degradation increases by partially replacement of the ethyl glycinate groups by small amounts... 

Polyelectrolyte complexes can be used as implants for medical use, as microcapsules, or for binding of pharmaceutical products, including proteins. In recent years, a new class of organometallic polymers, polyphosphazenes, has become available. Synthetic flexibility of polyphosphazenes makes them a suitable material for controlled-release technologies. Desirable characteristics of a polymeric system used for drug delivery are as follows ... 

Allcock, H.R., Polyphosphazenes as new biomedical and bioactive materials, in M. Chasin and R. Langer, Biodegradable Polymers as Drug Delivery Systems, New York Marcel Dekker, 1990 pp. 163-193. 

MAJOR APPLICATIONS Polymers have shown promise as bioerodible materials capable of (controlled degradation and sustained drug delivery for therapeutic cmd other related uses/ Polyphosphazenes have been evaluated for approximately two decades, but resecirch has become more focused in recent years. 

This chapter on polyphosphazenes provides the reader an overview of the synthesis and side group chemistry in context to the degradation profile and biocompatibility. In addition, it reviews the medical applications developed using biodegradable polyphosphazenes specifically drug delivery matrices and tissue-engineering scaffolds. 

Abstract A review is presented of the main types of bioresorbable or bioabsorbable materials used in medical applications such as drug delivery. Groups discussed include aliphatic polyesters, polyanhydrides, poly(ortho esters) (POE), polyphosphazenes, poly(amino acids) and pseudo poly(amino acids), polyalkylcyanoacrylates, poly(propylene fumarate) (PPF), poloxamers, poly(p-dioxanone) (PPDO) and polyvinyl alcohol (PVA). 

Aminated polyphosphazenes present amines with a low value of pKa as side groups, and constitute the most studied class of bioresorbable polyphosphazenes. Amino acid ester and imidazole-substituted polyphosphazenes appear to be two good candidates for drug delivery applications, because of their good hydrolysis degradation and low... 

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... 

Lakshmi, S., Katti, D. S. Laurencin, C. T. 2003. Biodegradable polyphosphazenes for drug delivery applications. Advanced Drug Delivery Reviews, 55, 467-482. 

Other polymers within the polycondensate group are also susceptible to hydrolysis and degrade predominantly via surface erosion. Polyorthoesters, polycarbonates and polyphosphazenes have been utilised on their own and as copolymers for drug delivery." ... 

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