Bioerodible polyanhydrides as drug‐carrier matrices. I: Characterization, degradation, and release characteristics

Abstract

Polyanhydrides based on a variety of aromatic and aliphatic dicarboxylic acids were developed as bioerodible carrier matrices for controlled delivery applications. The high hydrolytic reactivity of the anhydride linkage provides an intrinsic advantage over other classes of bioerodible polymers in versatility and control of degradation rates. For example, using the poly[bis(p-carboxyphenoxy) alkane anhydrides] as models, polymers with degradation rates in the range of 10(-1) to 10(-4) mg/h/cm2 were obtained by changing the alkane from a methyl to a hexyl group. The polymers were characterized by infrared (IR), differential scanning calorimetry, gel permeation chromatography, and scanning electron microscopy (SEM). Near zero-order degradation kinetics were observed for the hydrophobic polyanhydrides over several months. The drug release profile of the model drug p-nitroaniline followed closely that of the degradation of injection-molded poly[bis(p-carboxyphenoxy) propane anhydride] over a period of more than 8 months. Close correlation of polymer degradation and drug release was also observed in other injection-molded samples (10% loading), suggesting a release mechanism that was dominantly degradation controlled. Degradation of these polyanhydrides was pH sensitive, being enhanced in high pH, and became more stable in acidic conditions.

Molecular Description of Erosion Phenomena in Biodegradable Polymers

“…To estimate the degradation rate constants for CPH in the copolymer, we compare the molar erosion rate constants for poly(CPH) to that for poly(SA) reported by Leong et al 51,52 The ratio of the erosion rate constants for poly(SA) to that for poly(CPH) is used as a first approximation for the ratio of degradation rate constants for the SA-SA and CPH-CPH bonds, k SA-SA and k CPH-CPH , respectively. We then estimate the degradation rate constant for CPH in the copolymer, k CPH , as…”

Polymeric Delivery Systems for Biopharmaceuticals

“…Aliphatic polyanhydride homopolymers are often problematic materials as they are usually highly crystalline with unfavourable mechanical properties (Goepferich and Tessmar, 2002). Aromatic polyanhydrides erode slower than aliphatic ones (Leong et al, 1985), which is due to their increased hydrophobicity and the hindered approach of water to the anhydride bond (Tamada and Langer, 1992).…”

The Erosion Properties of Polyanhydrides

“…This is in contrast from what has been reported with the p(CPP:SA) polyanhydride. Leong et al [6] have reported that they could obtain a wide range of CPP erosion rates (1 week to several years) by increasing the monomer ratio of CPP to SA. However, Goepferich et al [7] have found that increasing CPP monomer content (although extending CPP release) does not actually affect SA release from p(CPP:SA).…”

“…Differential Scanning Colorimetry (DSC) studies indicate that the polymer degree of crystallinity decreases with increasing FAD monomer content [4] (see Figure 4). Hydrophobicity inhibits water penetration into the polymer matrix, but amorphous domains are more vulnerable to hydrolytic attack [6,7], and therefore degrade more easily than crystalline regions. These two opposing copolymer properties may compromise the range of degradation rates that can be achieved by varying the monomer ratio in the p(FAD:SA) copolymer.…”