Crosslinked polyanhydrides

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

Muggli, D. S., Burkoth, A. K. Anseth, K. S. (1999) Crosslinked polyanhydrides for use in orthopedic applications degradation behavior and mechanics. Journal of Biomedical Materials Research, 46, 271-278. 

Crosslinked polyanhydrides with three dimensional networks, showing high mechanical strength and a slow degradation rate. 

Another approach is the incorporation of acrylic functional groups in the monomeric unit. This leads to photocrosslinkable polyanhydrides. The mechanical strength and degradation rate of these crosslinked polyanhydrides depend on the nature of the monomeric species. 

The second type of polymer, unsaturated polyanhydrides of the structure [-(OOC-CH=CH-CO)x-(OOC-R-CO)y-]n, have the advantage of being able to undergo a secondary polymerization of the double bonds to create a crosslinked matrix. This is important for polymers requiring great strength, for instance. These polymers were prepared from the corresponding diacids polymerized either by... 

Cortisone acetate has been incorporated into several polyanhydrides (15). The rates of release of cortisone acetate from microcapsules of poly(terephthaUc acid), poly(terephthaUc acid-sebacic acid) 50 50, and poly(carboxyphenoxypropane-sebacic acid) 50 50 are shown in Fig. 8. These microcapsules were produced by an interfacial condensation of a diacyl chloride in methylene chloride with the appropriate dicarboxylic acid in water, with or without the crosslinking agent trimesoyl chloride. This process produces irregular microcapsules with a rough surface. The release rates of cortisone acetate from these microcapsules varied correspondingly with the rate of degradation of the respective polyanhydrides. It can be expected that the duration of release of cortisone acetate from solid microspheres, such as those produced by the hot-melt process, would be considerably longer. 

Crosslinking of amine- or hydroxy-terminated PAMAM dendrimers using cyclic anhydride - amine or cyclic anhydride - hydroxy addition reactions was employed for preparation of crosslinked thin films of very low permeability [73], Polyanhydrides, such as maleic anhydride-methyl vinyl ether copolymers, were used as crosslinking components. In the case of amine-terminated PAMAM, crosslinking and chemical stability were further increased by imidization of the maleamic acid groups retro-Michael eliminations were followed by Michael additions to further crosslink the film. 

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. 

The SA-FA copolymers displayed nearly constant degradation rates and drug release rates under physiological conditions. The time for complete degradation of poly(fumaric acid) and poly(sebacic acid) oecured in 2 and 15 days, respectively, while their copolymers degraded within this range. Radical copolymerization of styrene and methylmethacrylate with the polyanhydrides resulted in crosslinked insoluble polymers [40]. 

The physical and mechanical properties of polyanhydrides can be altered by modification of the polymer structure with a minor change in the polymer composition. Several such modifications include the formation of polymer blends, branched and crosslinked polymers, partial hydrogenation and reaction with epoxides. 

Many cyclic acid anhydrides are used industrially for crosslinking epoxy resins. These are mono-and polyanhydrides. Some typical, conunercially used anhydrides are shown. 

Figure 10.20 Schematic iiiustrations of in situ crosslinking of HBP (Boltorn H2004 ) in the PLA melt with the help of a polyanhydride (PA-18 (LV)) and related morphologies (up) as well as morphologies of tensile...

Unsaturated polyanhydrides exhibiting unsaturated bonds along the chain and thus being suitable for the synthesis of a crosslinked matrix. Unsaturated bonds remain intact during polymerization. 

Albertsson AC, Eklund M (1996) Short methylene segment crosslinks in degradable aliphatic polyanhydride network formation, characterization, and degradation. J Polym Sci Polym Chem 34 1395-1405... 

Li, H., Chen, Y, Xie, Y, 2003. Photo-crosslinking polymerization to prepare polyanhydride/ needle-like hydroxyapatite biodegradable nanocomposite for orthopedic application. Materials Letters 57, 2848-2854. 

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