Polyanhydrides structures

Biodegradable Polymers as Drug Carriers Table 5 Common polyanhydride structures... 

Fourier transform infrared (FTIR) spectroscopy and Raman spectroscopy have also been used to authenticate polyanhydride structures. Aliphatic polymers absorb at 1740 and 1810 cm while aromatic polymers absorb at 1720 and 1780 cm All the polyanhydrides show methylene bands because of deformation, stretching, rocking, and twisting. Aside from being used to ascertain polyanhydride structures, these techniques can be used to determine degradation progress, by monitoring the area of carboxylic acid peak (1770-1675 cm ) with respect to the characteristic anhydride peaks over time. 

Since the introduction of polyanhydrides to the regime of polymers, hundreds of polyanhydride structures have been reported. These polymers are divided into conventional and advanced polyanhydrides, with various subclasses under each category. Different classes of polyanhydrides with their structures and examples are given in Table 10.1. 

Since the introduction of polyanhydrides in the regime of polymers, himdreds of polyanhydride structures have been reported for the past century (23). A representative list of polyanhydrides is shown in Table 2. On the basis of their monomers, polyanhydrides can be categorized as the following types ... 

Polyanhydride structures can be modified by the addition of aminoacids, linked via imide bonds at the amino terminus, so that the carboxylic acid terminus remains available for the interaction with acetic anhydride [459]. These poly(anhydride-imides) degrade in a similar way as the simple polyanhydride polymers. Other modifications that can take place are copolymers linked with esters. In that way, the polymer contains two types of hydrolytically cleavable bonds. In the presence of water, both types of bonds are hydrolyzed, releasing the dicarboxylic acid and the ester [460]. An example of a poly(anhydride-ester) with application in the medicinal field includes sebacic acid and salicylic acid, a therapeutically useful compound. The release of sebacic acid in the body opens up a variety of potential applications. 

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). 

Several new series of polyanhydrides with advantageous properties for a variety of applications were also synthesized (8). The first ai e aliphatic-aromatic homopolyanhydrides of the structure... 

The second type of polymer, unsaturated polyanhydrides of the structure [-(OOC-CH=CH-CO)x-(OOC-R-CO)y-]n, have the advantage of being able to undergo a secondary polymerization of the double bonds to create a crosslinked matrix. This is important for polymers requiring great strength, for instance. These polymers were prepared from the corresponding diacids polymerized either by... 

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. 

Yet as the many sided debate went on, Wallace Carothers started a series of investigations in 1928 which would eventually establish the macromolecular concept. His objective from the beginning was to prepare polymers of known structure through the use of established reactions of organic chemistry (85). In the brilliant years before his untimely death in 1937, he studied the preparation and properties of polyesters, polyanhydrides, polyamides, and polychloroprene (28). 

Figure 2 Structure of polifeprosan 20, a polyanhydride-based excipient used for sustained-release of Carmustine, an antineoplastic agent.

Figure 5 General structure of polyanhydrides. R and R can be varied to modify degradation kinetics and profile. The lower frame shows the structure of P(CPP-SA), a polyanhydride copolymer, used in the Gliadel product. Abbreviations SA, sebacic acid CPP, carboxyphen-oxypropane.

Several review articles on biodegradable polymers and polyesters have appeared in the literature [12-22]. Extensive studies have been carried out by Al-bertsson and coworkers developing biodegradable polymers such as polyesters, polyanhydrides, polycarbonates, etc., and relating the structure and properties of aliphatic polyesters prepared by ROP and polycondensation techniques. In the present paper, the current status of aliphatic polyesters and copolyesters (block, random, and star-shaped), their synthesis and characterization, properties, degradation, and applications are described. Emphasis is placed primarily on aliphatic polyesters derived by condensation of diols with dicarboxylic acids (or their derivatives) or by the ROP of cyclic monoesters. Polyesters derived from cyclic diesters or microbial polyesters are beyond the scope of this review. 

Chemically-Controlled Systems. In these systems, the polymer matrix contains chemically-labile bonds. On exposure to water or enzymes the bonds hydrolyze, erode the three dimensional structure of the polymer and release the incorporated reagent into the surrounding medium. Depending on the polymer used, the erosion products may act as interferences, such as by altering the pH of the solution. Examples of these systems are polyglycolic acid (PGA) and a polyglycolic acid - polylactic acid (PGA/PLA) copolymer. PGA hydrolyzes to hydroxyacetic acid, and PGA/PLA hydrolyzes to lactic acid and hydroxyacetic acid. Other chemically-controlled systems are based on polyorthoesters, polycaprolactones, polyaminoacids, and polyanhydrides. 

Several combinations of monomers used to prepare polyanhydrides are classified as aliphatic, aromatic, aliphatic-aromatic, amine-based, and fatty acid-based polyanhydrides. The structures of these monomers determine... 

The second approach was applied in the synthesis of fatty acid terminated polyanhydrides. Polyanhydrides based on sebacic acid, and terminated with oleic, stearic, linoleic or lithocholic acid, or combinations of several fatty acids were synthesized 21). The general structure of fatty acid terminated polyanhydrides is shown in Figure 1. 

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