Polyanhydrides monomers

Within a series of closely related polyanhydride copolymers, the relative ratios of the two monomers have a marked effect on the rate of degradation of the resulting polymer. An example is shown in Fig. 

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. 

Various combinations of dicarboxylic acid derivatives and glycols enzymatically afforded polyesters under mild reaction conditions. Dicarboxylic acids as well as derivatives, activated and non-activated esters, cyclic acid anhydride, and polyanhydrides, were found to be useful as monomer for the enzymatic synthesis of polyesters. 

Polyanhydrides from Unsaturated and Fatty Acid-derived Monomers... 

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). 

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... 

Polyanhydrides have been modified by incorporating amino acids into im-ide bonds. The imide with the terminal carboxylic acids is activated with acetic anhydride and copolymerized with sebacic acid or CCP. Poly(anhydride-imides) increase the mechanical properties of the polyanhydrides. Degradation of poly(anhydride-imide)s is similar to that of polyanhydrides (i.e., surface erosion). Two different cleavable bonds (anhydride and ester) in the polymer chains have been included in polyanhydrides. Carboxylic acid-terminated e-caprolactone oligomers or carboxylic acid-terminated monomers (e.g., salicylic acid) have been polymerized with activated monomers (e.g., SA). 

Polyanhydrides, such as poly[bis(p-carboxyphenoxy)propane sebacic acid] copolymers (Figure 4.14), are also used for the fabrication of biodegradable implants. Polymer degradation occurs via hydrolysis, the biscarboxyphenoxypropane monomer is excreted in the urine and the sebacic acid monomer is metabolized by the liver and is expired as carbon dioxide via the lung (Figure 4.14). 

Gliadel is a biodegradable polyanhydride implant composed of poly[bis(p-carboxyphenoxy) propane sebacic acid] in a 20 80 monomer ratio, for the delivery of carmustine. The implant is indicated in the treatment of recurrent glioblastoma multiforme (GBM) which is the most common and fatal type of brain cancer. 

Polyanhydride Nanoparticles Polyanhydrides have been more commonly used to prepare microparticles than nanoparticles. However, the technology is adaptable for nanoparticles. The transfection efficiency of firefly luciferase DNA was enhanced when delivered in nanoparticles prepared from polyanhydride-lactic acid blends, demonstrating the potential application in gene delivery [120], The degradation and elimination of polyanhydrides have been reviewed [97], In vivo, the anhydride bond degrades to form diacid monomers that are eliminated from the body. 

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