Polyanhydrides, synthesis

Scheme 2. Polyanhydride synthesis via melt polycondensation involves first the formation of oligomeric acetylated prepolymers, followed by condensation under vacuum. Acetic acid is formed as a byproduct of the second reaction.

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). 

Domb, A.J. Ehrenfreund, T. Golenser, J. Langer, R. Israel, Z. Biodegradable polyanhydrides synthesis and drug delivery applications. Biodegrad. Polym. 2003,2, 121-151. 

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