Polyanhydrides anhydride groups

Polyanhydrides are characterized by anhydride bonds connecting monomers along the chain, or by anhydride groups located on the side of the chain and not along the backbone. Indeed, poly (malic anhydride) is a polyethylene chain with anhydride groups as side chains (Fig. 1.10). 

Sanders et al. (1999) attempted to lower the melting points of aromatic polyanhydrides by substituting branched alkyl groups in place of the linear alkyls of P(CPP-SA). They synthesized poly[l,2-bis(/ -carboxyphenoxy)-propane-co-sebacic acid] (P(1,2-CPP-SA)), poly[l,3-bis(/ -carboxyphenoxy)-2-methyl propane-co-sebacic anhydride] (P(CPMP-SA)), and poly[l,3-bis (/ -carboxyphenoxy)-2,2-dimethyl propane-co-sebacic anhydride] (P(CPDP SA)), all of which had melting points below 165°C. 

The analysis of 1H NMR spectra of aliphatic and aromatic polyanhydrides has been reported by Ron et al. (1991), and McCann et al. (1999) and Shen et al. (2002), and 13C NMR has been reported by Heatley et al. (1998). In 1H NMR, the aliphatic protons have chemical shifts between 1 and 2 ppm, unless they are adjacent to electron withdrawing groups. Aliphatic protons appear at about 2.45 ppm when a to an anhydride bond and can be shifted even further when adjacent to ether oxygens. Aromatic protons typically appear with chemical shifts between 6.5 and 8.5 ppm and are also shifted up by association with anhydride bonds. The sequence distribution of copolymers can be assessed, for example in P(CPH-SA), by discerning the difference between protons adjacent to CPH-CPH bonds, CPH SA bonds, and SA-SA bonds (Shen et al., 2002). FTIR and 111 NMR spectra for many of the polymers mentioned in Section II can be found in their respective references. 

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. 

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). 

Historically, polyanhydrides were synthesized for engineering materials. Because of their hydrolytical instability, these polyanhydrides have never been commercialized for engineering purposes. This instability has a beneficial aspect in drug delivery systems since the implant incorporated with an active drug does not need to be retrieved. The anhydride has a labile bond in the main chain of the polymer. This labile bond then breaks down into two carboxylic acid groups. 

Poly(anhydrides) are polymers containing the group -C(0)-0-C(0)- in their backbone. Several polyanhydrides such as poly(oxyisophthaloyl), poly(oxycarbonyl-1,4-phenylene methylene-1,4-phenylene carbonyl), poly(oxycarbonyl-1,4-phenylene isopropylidene-1,4-phenylene carbonyl), and poly(oxycarbonyl-1,4-phenylene isobutylidene-1,4-phenylene carbonyl) were synthesized with the expectation of good biodegradability. They do have good hydrolytic stability as opposed to aliphatic polyanhydrides [1]. The structures of these polymers are shown below. 

Polyanhydrides comprise monomer units connected by water-labile anhydride bonds. In the presence of water, the polymer is cleaved across the anhydride bond into two carboxylic acid groups (Fig. 1). It is precisely this hydrolytic instability that precluded their use in the textile industry in the 1950s and led researchers to suggest their potential as drug delivery carriers in the 1980s. Since then, polyanhydrides have been synthesized with a wide range of chemistries for a variety of biomedical applications. 

Higher olefin/maleic anhydride Polyanhydride Gulf Polymers with amine end groups, polyamides, etc. 

Polyanhydrides (. Elimination of water between carboxyl groups of a dicarboxylic acid can lead to the formation of polyanhydrides. The polymerization is best accomplished by reacting the dicarboxylic acid with acetic anhydride to form a mixed anhydride that is then heated under vacuum to eliminate acetic anhydride. The overall reaction is represented by Reaction 27. 

Polyorthoesters are a third class of biodegradable polymers that have been extensively investigated for dmg delivery applications.The degradable orthoester linkage is composed of a carbon bonded to three alkoxy groups. Polyorthoesters are generally more hydrophobic than polyesters and polyanhydrides, due to their lack of carbonyl functionality, and the intrinsic hydrolysis kinetics of the orthoester linkage is comparable to that of an anhydride. Polyorthoesters, therefore. 

Alternatively, acid-based polyanhydrides such as poly(fumaric anhydrides) and poly(maleic anhydrides) have raised interest because of the capacity of anhydrides to progressively hydrolyse in the presence of physiological fluids, leading to the production of high amounts of carboxylic groups on the surface of the dosage form, which have been shown to enhance bioadhesiveness of the matrix, thus increasing its residence time at the mucosal surfaces. 

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