The preparation of a complex of insulin–phospholipids and their interaction mechanism

Subcutaneous injections of insulin remain the standard treatment for insulin‐dependent diabetic patients, and noninvasive routes are studied but with little success. One of the reasons is that insulin is a hydrophilic compounds and is difficult to cross the mucosa barrier. In this paper, we developed a novel technique to fabricate the insulin–phospholipids complex by a solvent evaporation method with the aim of improving the lipophilicity of insulin. A systematic study on the preparation conditions of the insulin–phospholipids complex is reported in the present work. The formation mechanism and the physicochemical properties of the complex are studied. The associated efficiency of the phospholipids and insulin can be up to 100% when their mass ratio is 7.5 : 1 or more, and the solubility of the complex is improved more than 40 000 times compared with that of insulin alone in the n ‐octyl alcohol. The results of the insulin content in the complex and hypoglycemic effects in diabetic mice indicated that insulin was able to withstand the preparation procedure. The stability results showed that the complex was stable for 1 year at −20 °C. The interaction mechanism of this formation is that the peptide bonds of insulin interact with the water‐soluble head of phospholipids, forming a reverse micelle‐like structure. This novel complex will be of great importance in the drug delivery system for insulin via noninvasive routes. This method is cost effective, scalable, and can be used in many other peptide drugs. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.