Biocompatible microspheres based on acetylated polysaccharide prepared from water-in-oil-in-water (W1/O/W2) double-emulsion method for delivery of type II diabetic drug (exenatide)

Polysaccharide microspheres (PAMs) from acetylated pullulan were designed for the long-term delivery of peptide/protein drugs, as an alternative to a PLGA depot system. Three kinds of samples were obtained according to their different degrees of acetylation (0.8(PA1), 1.5(PA2), 2.3(PA3) acetyl groups in one glucose unit in pullulan), and then utilized to prepare a microsphere via a water-in-oil-in-water (W1/O/W2) emulsion method. The mean particle size of PAMs was shown to be in a range between 35 and 110 μm, as determined by a particle size analyzer. In order to evaluate their potential as a depot for protein/peptide delivery, exenatide, a drug used for the treatment of type II diabetes, was employed. The encapsulation efficiency of exenatide in PAMs was 69.1%, 80.4%, and 90.3% in PAM 1, PAM 2, and PAM 3, respectively. Although the release of exenatide from the PLGA microspheres evidenced a fast and high-burst behavior, PAMs evidenced a sustained release profile for 21 days. After 16 days, the released peptide was found to have a molecular weight almost identical to that of native exenatide, indicating that the stability of the peptide in the PAMs was maintained. The tissue reaction evidenced by the PAM was characterized by minimal foreign body reaction and minimal configurations of immune cells such as neutrophils and macrophages, but that of the PLGA microspheres was characterized by relatively elevated inflammation. On the basis of these results, we have concluded that the PAM may provide new insights into the development of new protein/peptide depots in long-term delivery.