SELF-ASSEMBLED HYDROGEL NANOPARTICLE OF CHOLESTEROL-BEARING PULLULAN AS A CARRIER OF PROTEIN DRUGS - COMPLEXATION AND STABILIZATION OF INSULIN

Insulin (Ins) spontaneously and easily complexed with the hydrogel nan oparticle of hydrophobized cholesterol-bearing pullulan (CHP) in water . The complexed nanoparticles (diameter 20-30 nm) thus obtained formed a very stable colloid. The thermal denaturation and subsequent aggreg ation of Ins were effectively suppressed upon complexation. The comple xed Ins was significantly protected from enzymatic degradation. Sponta neous dissociation of Ins from the complex was barely observed, except in the presence of bovine serum albumin. The original physiological a ctivity of complexed Ins was preserved in vivo after i.v. injection. ( C) 1998 Elsevier Science B.V. All rights reserved.