pH-sensitive nanoparticles for oral insulin delivery

摘要

The present invention discloses the pH-sensitive nanoparticles composed of pH-sensitive polymer, hydrophobic material, internal stabilizer, external stabilizer content and insulin drug. The present invention also includes a method for preparation of pH-sensitive nanoparticles, in particular, a multiple emulsions solvent evaporation method. The pH-sensitive nanoparticles of the present invention show good pH-sensitive property with 100-300 nanometer particle size. Significant decrease in blood glucose level is observed in streptozotocin (STZ)-induced diabetic rats and the bioavailability of insulin is more than 10% after oral administration of the insulin-loaded pH-sensitive nanoparticles.

主权项

1. A method of preparing pH-sensitive insulin-loaded nanoparticles comprising:
(a) mixing one part of insulin and two parts of an internal stabilizer to form solution A which is an internal water phase (W1); (b) dissolving one part of hydrophobic polymer with a molecular weight from 20,000 to 40,000 daltons and two parts of pH-sensitive polymer in a solvent of dichloromethane and acetone with a volume ratio of 4:1 to 3:1 to form solution B which is an oil phase (O); (c) forming solution C which is an external phase (W2) comprising an external aqueous stabilizer with a molecular weight from 31,000 to 50,000 daltons; (d) forming an initial emulsion (W1/O) comprising solution A obtained from (a) and solution B obtained from (b) by first ultrasonic emulsification; (e) forming a double emulsion (W1/O/W2) comprising the initial emulsion obtained from (d) and the external aqueous stabilizer of solution C obtained from (c) by second ultrasonic emulsification; (f) forming the pH-sensitive insulin-loaded nanoparticles by evaporation of the solvent, water washing, centrifugation of the nanoparticles, and freeze drying.