Polyanhydrides properties

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... 

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... 

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... 

B. Characterization of Thermal Properties, Crystallinity, and Phase Behavior of Polyanhydrides... 

It is important to characterize the thermal properties of polyanhydrides that are proposed for drug delivery applications, as changes in crystallinity... 

Biocompatibility is an essential property of new biomaterials for drug delivery. Biocompatibility is always assessed with respect to specific applications and may be assessed with respect to cytotoxicity, allergic responses, irritation, inflammation, mutagenicity, teratogenicity, and carcinogenicity (Katti el al., 2002). The reviews by Katti et al. (2002) and Domb et al. (1997) provide good discussions on the biocompatibility studies that have been conducted with polyanhydrides over the past two decades. 

The past two decades have produced a revival of interest in the synthesis of polyanhydrides for biomedical applications. These materials offer a unique combination of properties that includes hydrolytically labile backbone, hydrophobic bulk, and very flexible chemistry that can be combined with other functional groups to develop polymers with novel physical and chemical properties. This combination of properties leads to erosion kinetics that is primarily surface eroding and offers the potential to stabilize macromolecular drugs and extend release profiles from days to years. The microstructural characteristics and inhomogeneities of multi-component systems offer an additional dimension of drug release kinetics that can be exploited to tailor drug release profiles. 

Table I. Selected mechanical properties of bone and the crosslinked polyanhydrides [32,33]...

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). 

The property that makes polyanhydrides unique is their surface hydrophobic-ity. Due to this high hydrophobicity, polyanhydride matrices do not facilitate water absorption. Consequently, hydrolytic degradation is restricted to the surface—a property that is termed as surface erosion. This type of degradation allows for zero-order release of drugs, i.e., the drug release profile is independent of the residual concentration of the drug in the matrix. 

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. 

Recently, a new polyanhydride, poly(fatty acid-sebacic acid), has been synthesized. This polyanhydride uses hydrophobic dimers of erucic acid. Some of its physical properties relevant to the fabrication of drug delivery devices are also improved over those of the other anhydrides based on CPP lower melting temperature, higher solubility in solvents, and higher mechanical strength. The erosion of the polymers is dependent on... 

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). 

These polyanhydrides all possessed suitable properties including low melting points (60-82°C), biodegradability and pliability. These polyanhydrides were able to retain both hydrophilic (5FU) and hydrophobic (triamcinolone) drugs. The release of 5FU continued for almost 2 weeks and of triamcinolone for 3 weeks. 

Polyanhydrides are a class of bioerodible polymers that have shown excellent characteristics as drug delivery carriers. The properties of these biomaterials can be tailored to obtain desirable controlled release characteristics. Extensive research in this promising area of biomaterials is the focus of this entry. In the first part of the entry, the chemical structures and synthesis methods of various polyanhydrides are discussed. This is followed by a discussion of the physical, chemical, and thermal properties of polyanhydrides and their effect on the degradation mechanism of these materials. Finally, a description of drug release applications from polyanhydride systems is presented, highlighting their potential in biomedical applications. 

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