Aliphatic polyanhydrides, preparation

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. 

The development of unsaturated polyanhydrides responded to the necessity of improving the mechanical properties of the polymers in applications such as the temporary replacement of bone. " Unsaturated polyanhydrides, prepared by melt or solution polymerization, include homopolymers of fumaric acid (FA), acetylene-dicarboxylic acid (ACDA), and 4,4 -stilbenzenedi-carboxylic acid (STDA). The chemical structures of poly(FA) and poly(ACDA) are shown in Table 1. These polymers are highly crystalline and insoluble in common organic solvents. The double bonds of these monomers make them suitable for further crosslinking to improve mechanical properties of polyanhydrides. When copolymerized with aliphatic diacids, less crystalline polymers with enhanced solubility in chlorinated solvents result. 

The Synthesis of Polyanhydrides by Dehydrative Coupling. The synthesis of polyanhydrides was first reported in 1909 and led on to a series of aliphatic polyanhydrides being prepared in the 1930s, as potential materials for the textile industry. One method for the formation of such polyanhydrides, particularly where sensitive monomers are involved, is to find suit-... 

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... 

Typically, homopolymers are not studied because they possess unfavorable characteristics rendering their handling and manufacture difficult. Poly(SA), poly(CPP), and poly (FA) are semicrystalline and thus suffer from either being brittle or having high Tn,. Conversely, poly(FAD) is a liquid. Therefore, polyanhydrides are often prepared as copolymers of aliphatic and/or aromatic monomers. The most common copolymers under investigation in drug delivery applications include poly(FAD-SA) and poly(CPP-SA). 

Mallapragada et al. have prepared polyanhydrides, biodegradable polymers, from aliphatic and aromatic diacids under the action of microwave irradiation (Scheme 14.25) [54]. The reactions were performed in a household microwave oven. For this purpose, 0.49 mmol aliphatic or aromatic acid were mixed with 2.95 mmol acetic anhydride and irradiated at full power in a sealed borosilicate vial for 2 min. The anhydride was then removed by evaporation and the vial was irradiated for another 5 to 25 min. It was found that by use of this method it was possible to obtain polymers with number-average molecular weights (1700 to 11 300 g mol ) rather similar to those obtained under conventional conditions while reducing the reaction time from hours to 6-20 min. It was also possible to prepare copolymers of seba-cinic acid prepolymer and l,6-bis-(p-carboxyphenoxy)hexane. 

In the 1930 s, Carothers prepared a series of aliphatic poly(anhydride)s for potential use as fibers in the textile industry (1). However, the hydrolytic stability of these materials was very poor. By the mid-1950 s, Conix was able to synthesize aromatic poly(anhydride)s with improved film and fiber forming properties (2). Despite these properties, the polyanhydrides poor thermal and hydrolytic stability resulted in their limited use, and no conunercial applications were found. By the late 1960 s, however, hydrolytic instability became an important factor for polymers utilized in the manufacture of medical devices such as absorbable sutures and drug delivery systems. 

Polyanhydrides are among the most hydrolytically unstable polymers. These polymers were prepared first in 1909, subsequently investigated as potential textile fibers but found unstable melt-polycondensation. Here, starting from a dicarboxylic acid monomer, a prepolymer consisting of a mixed anhydride of the diacid with acetic acid is formed (Scheme 3). The polymer is obtained by subsequently heating the prepolymer under vacuum to eliminate the acetic anhydride by-product. Several aliphatic dicarboxylic acid compounds (sebacic acid (SA), fumaric acid (FA), etc.) and aromatic... 

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