Insulin containing polyethylenimine-dextran sulfate nanoparticles

An aqueous nanoparticle delivery system has been developed which employs the oppositely charged polymers polyethylenimine (PEI) and dextran Sulfate (DS) with zinc as a stabilizer. It is found that the pH Of PEI Solutions. tile weight ratio of the two polymers, and zinc sulfate concentrations all play significant roles in controlling particle size. Spherical particles of 250 run mean diameter were produced under optimal conditions which have a zeta potential of approximately +30 mV. Up to 90% drug entrapment efficiency was observed when insulin was used as a model protein drug. No degradation product, ere detected during in vitro dissolution or in potency studies. Circular dichroism (CD) spectra shocked no significant conformational changes compared to free insulin under optimized formulation conditions. Rapid release characteristic,, were observed in vitro dissolution studies. Biological actin 6, in steptozotocin-induced diabetic rats, however. exhibited a prolonged hypoglycemic effect. This system offers the following advantages: (1) ease of manufacturing under mild preparation conditions (2) employment of completely aqueous processing condition: (3) use Of biocompatible polymers which can be prepared aseptically : (4) ability to control particle size; (5) a high level of drug entrapment and (6) an ability to preserve protein secondary. Structure and biological activity. (C) 2003 Elsevier Science B.V. All rights reserved.