Amino-substituted polyphosphazenes

Synthesis and characterization of allyl amino-substituted polyphosphazenes were carried out using previously described techniques (8-10). Initially, the polymer shown in Figure 2, containing only 4-ethyl anilino substituents, was synthesized, characterized and exposed to varying doses of gamma radiation. 

It has been shown that allyl-amino substituted polyphosphazenes, specifically tailored to form glassy films from suitable solvents can be used for negative resist/mask applications for microlithography. As suggested by model studies, the addition of allylic double bonds to amino-substituted polyphosphazenes increases the sensitivity to radiation-induced crosslinking. However, it is probable that the stabilizing influence of the hindered amine substituent has reduced the graftabflity of these polymers. In addition, the inherent RIE resistance of the phosphazene family has been demonstrated, which underscores the possible usefulness of these systems for future resist work. Currently, other related... 

Table 2. Reactive Ion Etching Rates for Allyl-Amino Substituted Polyphosphazenes and Commercially Available Resist Materials (-250 V Bias, 40 SCCM, 900 mTorr, 0.08 W/cm )...

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... 

Synthetic approaches to produce polymers with desirable biomedical characteristics for this class of materials have been extensively reviewed (Allcock, 1990 Crommen et al, 1993). Poly[(amino acid ester) phos-phazenes] are knovm to be susceptible toward hydrolytic degradation and hold promise as degradable materials. Recently, Laurencin etal (1987) used a poly(imidazole methylphenoxy) phosphazene to study the release characteristics ofBSA. Protein release was demonstrated using C-labeled BSA in a 20% imidazole-substituted polyphosphazene. Release from this matrix consisted of an initial burst of almost 25% of the protein, followed by release over several hundred hours in which a total of 55% of the protein was released. Polymer degradation for the 20% imidazole-substituted polyphosphazene was also studied and found to be quite slow, with 4% of the polymer degraded in 600 hr. 

It has been clearly shown in many detailed studies that the substitution of adjacent bulky side groups, for example, at the a-C position of amino acid esters, shields the polyphosphazene backbone from the attack of water molecules resulting in more hydrolytically stable polymers (Figure 2.7). This provides a very simple method to tailor the rate of degradation of amino-acid-ester-substituted polyphosphazenes. For example, the glycine ethyl ester derivative is reported to degrade in around 3 months (half-life), the alanine derivative in 6 months, whilst the valine ethyl ester requires approximately 1 year to reach this level of degradation [26]. 

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... 

Up to now, nine classes of different polyphosphazenes are known and characterized substituted with aliphatic alcohols [40,41,262-281] or phenols [41,95, 277,282-297],with aliphatic [42,298-300] or aromatic [301-304] amino groups, with di-functional spiro hydroxy (e.g. dihydroxybiphenyl [305] or di hydroxy-... 

Amino, alkoxy, and aryloxy polyphosphazenes are typically prepared by nucleophilic displacement reactions of poly(dihalophosphazenes). Analogous reactions with organometallic reagents, however, result in chain degradation and cross linking rather than in linear, alkyl, or aryl substituted poly(phosphazenes). The thermolysis of appropriate silicon-nitrogen-phosphorus compounds can be used to prepare fully P—C bonded poly(organophosphazenes). The synthesis of two of these materials and their Si—N—P precursors is described here. 

In order to prepare hydrolytically stable polythionyiphosphazenes the perchlo-rinated polymers were reacted with nucleophiles to substitute the hydrolytically sensitive main group-element halogen bonds [2]. This type of post-polymerization structural modification is well-established in polyphosphazene chemistry [2,8]. Thus, aryloxide nucleophiles or primary amines were used to substitute the polymers leading to poly(aryloxythionylphosphazenes) 24 and poly(amino-thionylphosphazenes) 25 respectively [35,37] ... 

Goedemoed etal. (1988-1991) did use different polyphosphazene pohmers based on amino acid esters as substitutes on the polyphosphazene chain, to develop locally acting antitumor devices. A model anticancer agent, melphalan, was physically incorporated. The drug was incorporated into polymer microspheres by means of a solvent evaporation process. In vitro tumor models were used for the drug release studies. 

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