Aliphatic polyanhydrides copolymers

Polyanhydrides Polyanhydrides have a hydrophobic backbone with a hydrolytically labile anhydride linkage. These polymers widely vary in chemical composition and include aliphatic, aromatic, and fatty acid-based polyanhydrides. The rate of degradation depends on the chemical composition of the polymer. In general, aliphatic polyanhydrides degrade more rapidly than the aromatic polymer. Hence, copolymer blends with varying ratios of aliphatic-to-aromatic polyanhydrides can be synthesized to suit specific applications. 

The melting point, as determined by differential scanning calorimeter, of these aromatic polyanhydrides is mnch higher than aliphatic polyanhydrides. The melting point of aliphatic-aromatic copolyanhydrides is proportional to aromatic content. For this type of copolymers, there is characteristically a minimnm between 5 and 20mol% of lower-melting component. The introdnction of fatty acids in the copolymer chain lowers the melting point as compared to that of bulk polymer [14]. 

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]. 

Owing to their pronounced hydrolytic instability, polyanhydrides have therefore been explored as degradable implant materials. Aliphatic polyanhydrides degrade within days whereas some aromatic polyanhydrides degrade over several years. Thus, aliphatic-aromatic copolymers, having intermediate rates of degradation, are usually employed. 

The effect of y-irradiation on polyanhydrides for sterilization purposes has been studied (Mader et al, 1996). Aliphatic and aromatic homo- and copolymers were y-irradiated at a 2.5 Mrad dose under dry ice and the properties of the polymer before and after radiation were monitored. All polymers did not change in physical or mechanical properties and their iH-NMR and IR spectra remain the same. A slight increase in molecular weight was found for aliphatic polyanhydrides. 

The melting points of a large number of polymers have been determined and are shown in Table 2. Aliphatic polyanhydrides generally melt at lower temperatures than do aromatic polyanhydrides. The melting point of aromatic-aliphatic copolymers is proportional to the aromatic content in the copolymer. Introduction of fatty acids in copolymers also lowers the melting point of the bulk polymer. 

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. 

Typically, homopolymers are not studied because they possess unfavorable characteristics rendering their handling and manufacture difficult. Poly(SA), poly(CPP), and poly (FA) are semicrystalline and thus suffer from either being brittle or having high Tn,. Conversely, poly(FAD) is a liquid. Therefore, polyanhydrides are often prepared as copolymers of aliphatic and/or aromatic monomers. The most common copolymers under investigation in drug delivery applications include poly(FAD-SA) and poly(CPP-SA). 

The stability of polyanhydrides in a solution was studied using chloroform under dry nitrogen atmosphere at 37°C.f The aromatic polyanhydrides remained stable under these conditions during a three-day period, while copolymers with aliphatic S A had a significant molecular weight loss during the same time period. Therefore, polyanhydrides can be processed in a solution environment as long as the time is not extended more than this period. 

Mallapragada et al. have prepared polyanhydrides, biodegradable polymers, from aliphatic and aromatic diacids under the action of microwave irradiation (Scheme 14.25) [54]. The reactions were performed in a household microwave oven. For this purpose, 0.49 mmol aliphatic or aromatic acid were mixed with 2.95 mmol acetic anhydride and irradiated at full power in a sealed borosilicate vial for 2 min. The anhydride was then removed by evaporation and the vial was irradiated for another 5 to 25 min. It was found that by use of this method it was possible to obtain polymers with number-average molecular weights (1700 to 11 300 g mol ) rather similar to those obtained under conventional conditions while reducing the reaction time from hours to 6-20 min. It was also possible to prepare copolymers of seba-cinic acid prepolymer and l,6-bis-(p-carboxyphenoxy)hexane. 

These are the copolymers of aromatic and aliphatic diacid monomers. Polyanhydrides of diacid monomers containing poly(lactic acid) (PLA) and poly(hydroxybutyrate) (PHB) are synthesized by either melt or solution with molecular weights of up to 44,600 [17,18]. They were found to be less crystalline in nature and possessed slow degradation due to their aromatic content. 

Unsaturated homopolymers are crystalline and insoluble in common organic solvents, whereas copolymers with aliphatic diacids are less crystalline and soluble in chlorinated hydrocarbons. The unsaturated polyanhydrides also provide a means for cross-linking through the double bonds that remain intact during the polymerisation process, and thus their mechanical properties can be improved (Domb et al., 1991). 

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