STABILITY OF ATRIOPEPTIN-III IN POLY(D,L-LACTIDE-CO-GLYCOLIDE) MICROSPHERES

The stability of atriopeptin III (APIII) encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) microspheres has been investigated and compared to the stability of APIII alone. When the microspheres are shaken in Tris-buffered Ringer's (pH 7.4) at 40-degrees-C, the APIII inside of the microspheres is completely degraded in 5 days. Though APIII is stable in microspheres that are stored desiccated at -20-degrees-C, when the microspheres are stored in 95% relative humidity at 40-degrees-C there is 20% degradation of APIII in 8 days. Concentrated APIII, on the other hand, shows no degradation after 2 weeks at 40-degrees-C and dilute APIII in water shows no loss after 1 month at 40-degrees-C. In Tris-buffered Ringer's (pH 7.4) at 40-degrees-C, however, dilute APIII degrades with a half life of 8.7 days unshaken or 2.4 days when shaken. The pattern of degradation peaks seen during HPLC analysis of samples degraded in the presence of PLGA is different than that seen when APIII alone degrades in buffer solution. These experiments indicate that PLGA may not be an appropriate polymer for use with some peptides and proteins.