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, the weight ratio of the two polymers, and zinc sulfate concentrations all play significant roles in controlling particle size. Spherical particles of 250 nm 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 products were detected during in vitro dissolution or in potency studies. Circular dichroism (CD) spectra showed no significant conformational changes compared to free insulin under optimized formulation conditions. Rapid release characteristics were observed in in vitro dissolution studies. Biological activity 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 conditions; (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.
Tiyaboonchai
Waree
W
Department of Pharmaceutical Chemistry, School of Pharmacy, The University of Kansas, 2095 Constant Ave., Lawrence, KS 66047-3729, USA.
Woiszwillo
James
J
Sims
Robert C
RC
Middaugh
C Russell
CR
D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose / Q000032:analysis; D002942:Circular Dichroism; D016264:Dextran Sulfate / Q000737:chemistry*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy; D004355:Drug Stability; D005612:Freeze Drying; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D008863:Microspheres; D036103:Nanotechnology; D010316:Particle Size; D011094:Polyethyleneimine / Q000737:chemistry*; D017433:Protein Structure, Secondary; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013499:Surface Properties
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D011094:Polyethyleneimine; D016264:Dextran Sulfate