Polyelectrolyte complex of chondroitin sulfate and peptide with lower p I value in poly(lactide-co-glycolide) microsphere for stability and controlled release

Abstract

A polyelectrolyte complex between a therapeutic peptide and chargeable polymer was applied to prevent peptide denaturation in poly(lactide-co-glycolide) (PLGA) microspheres. Chondroitin sulfate A (CsA) was employed as a polymeric additive for the formation of an ionic complex with insulin (InS). The complex prepared at pH 3.0 evidenced a nano-size in the range of 100–400 nm with a mono distribution. The stability of InS in the complex in an organic/water (O/W) interface was verified via RP-HPLC. The insulin in the complex evidenced a retention time almost identical to native InS, whereas free insulin did not evidence such a retention time. On the basis of these studies, PLGA microspheres including a complex with various CsA/InS ratios were prepared via a double-emulsion method (PLGA/CsA MS). InS loading efficiency in the system is higher than that of the microspheres without CsA. The system evidenced a lower initial burst and, following the initial burst, continuous release kinetics for 30 days. Circular dichroism (CD) spectra demonstrated that the insulin in PLGA/CsA MS is more stable than the PLGA-only microspheres (PLGA/only MS) for 20 days. These results indicate that the complex system with CsA is useful for the long-term delivery of peptides with lower p I values.