Effective incorporation of insulin in mucus permeating self-nanoemulsifying drug delivery systems.

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V

PubMedID: 25933940

Karamanidou T, Karidi K, Kammona O, Kiparissides C. Effective incorporation of insulin in mucus permeating self-nanoemulsifying drug delivery systems. Eur J Pharm Biopharm. 2015;.
The development of a novel, mucus permeating SNEDDS formulation for oral insulin delivery containing a hydrophobic ion pair of insulin/dimyristoyl phosphatidyl glycerol (INS/DMPG) is presented. Three oil/surfactant/cosurfactant combinations and 27 weight ratios of oil, surfactant and cosurfactant for each combination were evaluated with the aid of ternary phase diagrams, for the incorporation of the protein/phospholipid complex. The developed formulation was characterized by an average droplet diameter of 30-45nm. Depending on the initial protein concentration, the loading of insulin in SNEDDS varied between 0. 27 and 1. 13wt%. The therapeutic protein was found to be efficiently protected from enzymatic degradation by intestinal enzymes (i. e. , trypsin, a-chymotrypsin). The SNEDDS formulation exhibited increased mucus permeability and did not appear to be affected by ionic strength. The incorporation of INS/DMPG in SNEDDS prevented an initial burst release of insulin. INS/DMPG loaded SNEDDS were found to be non-cytotoxic up to a concentration of 2mg/ml. According to the reported results, the incorporation of the hydrophobic ion pair of INS/DMPG in SNEDDS could be regarded as a promising strategy for the oral delivery of insulin.