Preparation and release characteristics of insulin and insulin-like growth factor-one from polymer nanoparticles

Abstract

Two methods of preparing polymer nanoparticles containing (a) insulin and (b) insulin-like growth factor-1 were compared and the influence of process parameters on size and release characteristics was determined. Poly(lactide-glycolide)co-polymer (50:50) was used in both methods. Method one used a salting-out process; while method two used a solvent evaporation/double emulsion procedure forming a w/o/w secondary emulsion. Particles were separated by centrifugation and dried under vacuum. Particle size was analysed by scanning electron microscopy and protein release by dissolution and high pressure liquid chromatography. Method one produced particles of diameter 0.3–0.8 µm, whereas method two gave larger particles of 0.76–1.05 µm and in both procedures reducing pH also decreased particle size. Optimal emulsifying speed was below 4 000 rpm and scanning electron micrographs showed smooth spherical particles. Release characteristics of insulin and IGF-1 in method one and two were similar releasing 60% in 10 days but in method one release was diminished to 8% over a similar time period. Method one proved successful in producing spheres of the required size range but hampered protein loading by denaturation resulting in a low release rate. Method two provided an acceptable release rate but produced particles with diameters of about one micron.

Key Words: :

• Nanoparticles
• poly(lactide-glycolide)co-polymer
• insulin
• insulin-like growth factor-1
• sustained release