Insulin-loaded nanoparticles are prepared by alginate ionotropic pre-gelation followed by chitosan polyelectrolyte complexation.
Alginate nanoparticles were prepared from dilute alginate sol by inducing a pre-gel with calcium counter ions, followed by polyelectrolyte complex coating with chitosan. Particles in the nanometer size range were obtained with 0.05% alginate and 0.9 mM Ca2+. The mean particle size was influenced by time and stirring speed of nanoparticle preparation, by alginate guluronic acid content and chitosan molecular weight and by the initial alginate:chitosan mass ratio. The association efficiency of insulin into alginate nanoparticles, as well as loading capacity were mainly influenced by the alginate:chitosan mass ratio. Under optimized size conditions, the association efficiency and loading capacities were as high as 92% and 14.3%, respectively. Approximately 50% of the protein was partially retained by the nanoparticles in gastric pH environment up to 24 hours while a more extensive release close to 75% was observed under intestinal pH conditions. Mild formulation conditions, optimum particle size range obtained, high insulin entrapment efficiency, and resistance to gastrointestinal release seem to be synergic and promising factors toward development of an oral insulin delivery form.
Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Porto, Porto, Portugal.
B
B
Sarmento
A J
AJ
Ribeiro
F
F
Veiga
D C
DC
Ferreira
R J
RJ
Neufeld
D000085:Acetates / Q000737:chemistry; D000464:Alginates / Q000737:chemistry*; D002118:Calcium / Q000737:chemistry; D002122:Calcium Chloride / Q000737:chemistry; D048271:Chitosan / Q000737:chemistry*; D016503:Drug Delivery Systems; D004573:Electrolytes / Q000737:chemistry*; D005782:Gels; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000737:chemistry / Q000378:metabolism*; D007477:Ions; D008855:Microscopy, Electron, Scanning; D053761:Nanocomposites / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry
D000085:Acetates; D000464:Alginates; D004573:Electrolytes; D005782:Gels; D007328:Insulin; D007477:Ions; D011108:Polymers; D048271:Chitosan; D002122:Calcium Chloride; D002118:Calcium