Poly(ester-anhydrides) Derived from Esters of Hydroxy Acid and Cyclic Anhydrides

The alternating architecture and hydrophobic side chains hinder hydrolytic cleavage and anhydride interchange in poly(sebacic acid-ricinoleic acid) (P(SA-RA)), which provides stable polyanhydrides at room temperature. In this report, a series of polyanhydrides were designed to investigate the effect of ester bonds, hydrophobic side chains, phenyl moieties, and their distance from anhydride bonds on their stability and properties. Polyanhydrides with alternating architecture are constructed by the polymerization of ester-diacids prepared from ricinoleic or other hydroxy acids with anhydrides such as succinic, maleic, and phthalic anhydrides. The hydrophobic side chains are designed closer to anhydride bonds to investigate hindrance to hydrolytic cleavage and anhydride interchange. Polyanhydrides were obtained by the activation of ester-diacid using acetic anhydride followed by melt condensation. The reactions were monitored by NMR, Fourier transform infrared (FTIR), and gel permeation chromatography (GPC). The synthesized poly(ester-anhydride)s with a shorter chain length compared to P(SA-RA) were stable at room temperature. The hydrolytic degradation studies reveal that the phenyl moiety present in poly(ricinoleic acid phthalate) (PRAP) and poly(hydroxystearic acid phthalate) (PHSAP) reduces the hydrolysis of anhydride bonds. Poly(hydroxyoctanoic acid succinate) (PHOAS) demonstrates the highest molecular weight of all tested polymers. The results reveal that the presence of hydrophobic side chains, phenyl moieties, and their distance from anhydride bonds significantly improves the stability. These stable polyanhydrides can provide convenience to use in control drug-delivery applications. The in vitro drug release study using ibuprofen shows that polymers with aromatic units such as PRAP and PHSAP establish sustained release, which presents more than 50 and 40% of ibuprofen over a period of 28 days.