Polyanhydrides poly

A considerable number of non-cross-linked aromatic and heterocyclic polymers has been produced. These include polyaromatic ketones, aromatic and heterocyclic polyanhydrides, polythiazoles, polypyrazoles, polytriazoles, poly-quinoxalines, polyketoquinolines, polybenzimidazoles, polyhydantoins, and polyimides. Of these the last two have achieved some technical significance, and have already been considered in Chapters 21 and 18 respectively. The most important polyimides are obtained by reacting pyromellitic dianhydride with an aromatic diamine to give a product of general structure (Figure 29.17). 

Cortisone acetate has been incorporated into several polyanhydrides (15). The rates of release of cortisone acetate from microcapsules of poly(terephthaUc acid), poly(terephthaUc acid-sebacic acid) 50 50, and poly(carboxyphenoxypropane-sebacic acid) 50 50 are shown in Fig. 8. These microcapsules were produced by an interfacial condensation of a diacyl chloride in methylene chloride with the appropriate dicarboxylic acid in water, with or without the crosslinking agent trimesoyl chloride. This process produces irregular microcapsules with a rough surface. The release rates of cortisone acetate from these microcapsules varied correspondingly with the rate of degradation of the respective polyanhydrides. It can be expected that the duration of release of cortisone acetate from solid microspheres, such as those produced by the hot-melt process, would be considerably longer. 

The stability of polyanhydrides composed of the diacids sebacic acid (SA), bis( -carboxyphenoxy)methane (CPM), l,3-bis(g-carboxyphe-noxy)propane (CPP), l,6-bis( -carboxyphenoxy)hexane (CPH), and phenylenedipropionic acid (PDP), in solid state and in organic solutions, was studied over a 1-year period. Aromatic polyanhydrides such as poly(CPM) and poly(CPH) maintained their original molecular weight for at least a year in both solid state and solution (20). 

In contrast, aliphatic polyanhydrides such as poly(SA) and poly-(PDP) decreased in molecular weight over time. The decrease in molecular weight shows first-order kinetics, with activation energies... 

Implants in the rabbit corneas exhibited no observable inflammatory characteristics over a period of 6 weeks. Compared to other previously tested polymers, the inertness of these polyanhydrides rivals that of the biocompatible poly(hydroxyethyl methacrylate) and ethylene-vinyl acetate copolymer. Histological examination of the removed corneas also revealed the absence of inflammatory cells (21)... 

Polyester synthesis was carried out hy insertion-dehydration of glycols into polyanhydrides using lipase CA as catalyst (Scheme 6). The insertion of 1,8-octanediol into poly(azelaic anhydride) took place at 30-60°C to give the corresponding polyester with molecular weight of several thousands. Effects of the reaction parameters on the polymer yield and molecular weight were systematically investigated. The dehydration reachon also proceeded in water. The reaction behaviors depended on the monomer structure and reaction media. 

Polyanhydrides Polyorthoesters Poly(amino acids) Psuedopolyamino acids Polyphosphazenes... 

Polyanhydrides based on unsaturated and fatty acid-derived monomers are shown in Table III. Poly(fumaric acid) (PFA) was fist synthesized by Domb et al. (1991) by both melt polycondensation and solution polymerization. The copolymer of fumaric acid and sebacic acid (P(FA-SA)) has been synthesized and characterized (Domb et al., 1991 Mathiowitz et al., 1990b). The mucoadhesive properties of this polymer... 

Fatty acids have also been converted to difunctional monomers for polyanhydride synthesis by dimerizing the unsaturated erucic or oleic acid to form branched monomers. These monomers are collectively referred to as fatty acid dimers and the polymers are referred to as poly(fatty acid dimer) (PFAD). PFAD (erucic acid dimer) was synthesized by Domb and Maniar (1993) via melt polycondensation and was a liquid at room temperature. Desiring to increase the hydrophobicity of aliphatic polyanhydrides such as PSA without adding aromaticity to the monomers (and thereby increasing the melting point), Teomim and Domb (1999) and Krasko et al. (2002) have synthesized fatty acid terminated PSA. Octanoic, lauric, myristic, stearic, ricinoleic, oleic, linoleic, and lithocholic acid acetate anhydrides were added to the melt polycondensation reactions to obtain the desired terminations. As desired, a dramatic reduction in the erosion rate was obtained (Krasko et al., 2002 Teomim and Domb, 1999). 

Sanders et al. (1999) attempted to lower the melting points of aromatic polyanhydrides by substituting branched alkyl groups in place of the linear alkyls of P(CPP-SA). They synthesized poly[l,2-bis(/ -carboxyphenoxy)-propane-co-sebacic acid] (P(1,2-CPP-SA)), poly[l,3-bis(/ -carboxyphenoxy)-2-methyl propane-co-sebacic anhydride] (P(CPMP-SA)), and poly[l,3-bis (/ -carboxyphenoxy)-2,2-dimethyl propane-co-sebacic anhydride] (P(CPDP SA)), all of which had melting points below 165°C. 

The synthesis of poly(anhydride-co-amide)s (Table VII) of various chemistries was pursued by Hartmann and Schulz (1989) as a means of improving biocompatibility and extending the degradation times of polyanhydrides. This work also contains calorimetry data on the thermal transitions and spectroscopic characterization. 

Jiang and Zhu (2001) became interested in synthesizing additional polyanhydrides with fluorescence after their discovery of the fluorescent properties of PCPS. They synthesized the series of poly(anhydride-co-amide)s poly p-[carboxyphenoxy(ethyl/propyl/butyl)formamido]benzoic anhydride (PCEFB, PCPFB, and PCBFB) (Jiang et al., 2001c). Only the ethyl polymer emitted strong fluorescence, which was consistent with their previous study of the poly(anhydride-co-ester)s of similar chemistry... 

Biodegradable polymers, both synthetic and natural, have gained more attention as carriers because of their biocompatibility and biodegradability and therewith the low impact on the environment. Examples of biodegradable polymers are synthetic polymers, such as polyesters, poly(orfho-esters), polyanhydrides and polyphosphazenes, and natural polymers, like polysaccharides such as chitosan, hyaluronic acid and alginates. 

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