Synthesis and in-vitro drug release of insulin-loaded poly(n-butyl cyanoacrylate) nanoparticles

Nanoparticles have been prepared by dispersion polymerisation of n-butyl cyanoacrylate in acidified water, with and without the inclusion of insulin. The molecular weight of polymerising material increased by a stepwise process, in which chains are initiated, terminated, and reinitiated, until an equilibrium molecular weight is reached. This equilibrium molecular weight is higher at lower dispersion pH. The reaction is complete within two hours. Insulin is capable of initiating polymerisation, but if introduced after all of the monomer has been incorporated into growing nanoparticles it has no effect on polymer molecular weight. A drug loading of 72% was achieved in particles produced at 25 degrees C and pH 3.0, with insulin introduced one hour after monomer initiation. Particle degradation characteristics were assessed using solutions of esterase in phosphate buffered saline at pH 7.0, with butanol release monitored as a measure of polymer degradation. Insulin realease was monitored under the same conditions. Both butanol production and insulin release showed a similar biphasic mechanism, indicating that the drug release rate is determined by polymer degradation characteristics. An initial burst release of both materials is associated with the degradation of surface species, and this is then followed by a steady-state release from sub-surface material. Insulin release as a function of time at an esterase concentration of 2.0 mg.ml(-1).