Polyanhydrides Used in Drug Delivery

We have already mentioned a few of the polyanhydride chemistries that have been studied in drug delivery applications. Tables II through VII present some of the polyanhydrides that have been explored for drug 

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). 

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Biocompatible ortho aromatic polyanhydrides, (IV), prepared by Uhrich [5] were used in drug delivery systems and as scaffolding implants for tissue reconstruction. 

Based on the above reasons, polymers possessing a variety of degradation rates and mechanisms have been developed however, hydrolysis still remains the predominant degradation mechanism for polymers that are most commonly used in drug delivery applications. Many polymers that are susceptible to hydrolysis, for example, the polyesters PLA and PLG, degrade by random hydrolysis that takes place homogeneously throughout the bulk of the polymer device. In contrast, other classes of polymers, such as the polyanhydrides and polyorthoesters, have been developed in an attempt to yield hydrolysis only at the outer surface of the device that is exposed directly... 

Synthetic polymers have recently been examined for use in drug delivery systems. Polyesters, polyurethanes and polyanhydrides are among some of these synthetic polymers [3]. 

Aromatic and aliphatic polyanhydrides, especially sebacic acid-derived ones, are usually copolymerized with other classes of polyanhydrides or conjugated with fatty acids to be used in drug delivery [461-463], They are studied for their use in the treatment of various disease conditions such as cancer, osteomyehtis, local infections, restenosis [464], eye disorders and Alzheimer s disease [465], They are also used in local anaesthesia and in gene delivery [466,465],... 

Poly(ortho esters) (XVII) contain acid-labile linkages in the polymer backbone. As with the polyanhydrides discussed above, poly(ortho esters) are a class of polymers that can degrade heterogeneously by surface erosion. These polymers lose material from the surface only, while retaining their original geometry. As such, their primary use is in drug delivery. 

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... 

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