Effects of incorporated drugs on degradation of novel 2,2'-bis(2-oxazoline) linked poly(lactic acid) films

Earlier studies have indicated that the degradation rate of poly(lactic acid) (PDLLA) can be modified by using 2,2′-bis(2-oxazoline) as a chain extender in polymer synthesis to form a lactic acid-based poly(ester-amide) (PEA). In the present study, the effect of an incorporated drug on the degradation rate of the PEA was evaluated. The model drugs, neutral guaifenesin, acidic sodium salicylate (pK_a 3.0) and basic timolol (pK_a 9.2), were incorporated into solvent cast PDLLA and PEA films. The drug content in the films was 2% (w/w). The degradation studies were carried out in PBS (pH 7.4, 37 °C); the resulting decrease in molecular weight of polymers was determined by size exclusion chromatography and the weight loss of films was measured. In addition, the drug release from the films in PBS (pH 7.4, 37 °C) was studied. The model drugs were released from the PDLLA and PEA films in a biphasic or triphasic manner. The final fast release phase of the drugs from both PDLLA and PEA films started when the molecular weight (M_n) of the polymer had decreased close to 15,000 g/mol. The degradation rate of the PDLLA films was clearly enhanced by incorporated sodium salicylate or timolol. Whereas, the degradation rate of the PEA film was not enhanced by the incorporated drugs. The present results indicate that when compared to the PDLLA film, degradation rate of the PEA film in the presence of the drug is more predictable.