Polyanhydrides solubility

Several of the synthetic efforts outlined in Section II were motivated partially by the necessity of increasing the processability of polyanhydrides. Solubilities of the 20 80 copolymers of P(CPP SA) and P(FAD SA) are compared by Domb and Maniar (1993). They reported improved solubility of the later over former in several organic solvents including (in order of decreasing solubility) THF, 2-butanone, 4-methyl-2-pentanone, acetone, and ethyl acetate. 

Polyanhydrides Synthetic Melt condensation, ring-opening polymerization Most polyanhydrides soluble in organic solvents, insoluble in water... 

Lucas, P. A., Laurencin, C., Syftestad, G. T., Domb, A., Goldberg, V. M., Caplan, A. I., and Langer, R., Ectopic induction of cartilage and bone by water-soluble proteins from bovine bone using a polyanhydride delivery vehicle, J. Control. Rel. In Press. 

As pointed out by Heller (2), polymer erosion can be controlled by the following three types of mechanisms (1) water-soluble polymers insolubilized by hydrolytically unstable cross-links (2) water-insoluble polymers solubilized by hydrolysis, ionization, or protonation of pendant groups (3) hydrophobic polymers solubilized by backbone cleavage to small water soluble molecules. These mechanisms represent extreme cases the actual erosion may occur by a combination of mechanisms. In addition to poly (lactic acid), poly (glycolic acid), and lactic/glycolic acid copolymers, other commonly used bioerodible/biodegradable polymers include polyorthoesters, polycaprolactone, polyaminoacids, polyanhydrides, and half esters of methyl vinyl ether-maleic anhydride copolymers (3). 

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... 

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. 

Anastasiou, T.J. Uhrich, K.E. Novel polyanhydrides with enhanced thermal and solubility properties. Macromolecules 2000, 33 (17), 6217-6221. 

Aromatic homopolyanhydrides are insoluble in common organic solvents and melt at high temperatures (Table 1). These properties limit the use of purely aromatic polyanhydrides, since they can not be fabricated into films or microspheres using solvent or melt techniques. Synthesis of soluble and low melting copolymers of common aromatic diacids have been recently reported [53, 54]. 

In a recent US patent, Ziegast described a series of polyanhydrides (of the formula shown below) which are useful for controlled drug delivery of drugs [55]. These polymers have a similar structure to the polymers synthesized by Conix (Table 1) [11, 12], but with different chain structures between the two aromatic rings. The polymers were soluble in chlorinated hydrocarbons with a Tg ranging from 6 to about 90 °C. The in vitro degradation in phosphate buffer of these polymers is about 100 days with a lag time of up to 30 days for some polymers [55]. If these homopolymers are implanted in animals, they will produce large diacid monomers which have to be eliminated from the body. 

The majority of polyanhydrides dissolve in solvents such as dichloromethane and chloroform. However, the aromatic polyanhydrides exhibit much lower solubility than aliphatic polyanhydrides. But the copolymers of two different aromatic monomers showed increased solubility with a decrease in T [15]. 

Aliphatic polyanhydrides synthesized lirom saturated diacid monomers are crystalline, melt at tanperatuies below 100 °C, and are soluble in chlorinated hydrocarbons. They are degraded and eliminated from the body within weeks [39],... 

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