Polyanhydrides degradation

FIGURE 1 Rate of polyanhydride degradation versus time. PCPP and SA copolymers were formulated into 1.4-cm-diameter disks 1 mm thick by compression molding, and placed into a 0.1 M pH 7.4 phosphate buffer solution at 37°C. The cumulative percentage of the polymer which degraded was measured by absorbance at 250 nm. 

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 Polyanhydrides have a hydrophobic backbone with a hydrolytically labile anhydride linkage. These polymers widely vary in chemical composition and include aliphatic, aromatic, and fatty acid-based polyanhydrides. The rate of degradation depends on the chemical composition of the polymer. In general, aliphatic polyanhydrides degrade more rapidly than the aromatic polymer. Hence, copolymer blends with varying ratios of aliphatic-to-aromatic polyanhydrides can be synthesized to suit specific applications. 

Polyanhydrides degrade primarily by surface erosion and possess excellent in vivo compatibility. In 1996 the FDA approved a polyanhydride-based drug delivery system to the brain of chemotherapeutic agent BCNU, which is currently being manufactured by Guilford Pharmaceutical, Inc. 

Polyanhydrides are among the most reactive and hydrolytically unstable polymers currently used as biomaterials. Their high chemical reactivity is an advantage, as polyanhydrides degrade by surface erosion without the need to incorporate various catalysts into the device formulation, the major drawback being the potential reactivity of the polymer matrix toward nucleophiles, which limits the drugs that can be successfully incorporated. 

Owing to their pronounced hydrolytic instability, polyanhydrides have therefore been explored as degradable implant materials. Aliphatic polyanhydrides degrade within days whereas some aromatic polyanhydrides degrade over several years. Thus, aliphatic-aromatic copolymers, having intermediate rates of degradation, are usually employed. 

Gopferich, A., TeBmar, J., 2002. Polyanhydride degradation and erosion. Advanced Drug Dehvery Reviews 54, 911—931. 

Polyanhydrides degrade by hydrolytic cleavage of the anhydride bonds at a well predicted rate and are completely removed from the body within the period of a few weeks. Polyanhydrides are reported to ultimately xmdergo heterogeneous surface erosion, which is favored by the water lability of its anhydride bonds and the hydrophobic-ity of its surface. The extent of hydrophobicity of the polymer is based on the ratio of the monomer units used and makes it water impermeable, thus more stable. 

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