Systemic delivery of insulin via the nasal route using a new microemulsion system: In vitro and in vivo studies

The main purpose of this study was to investigate the nasal absorption of insulin from a new microemulsion spray preparation in rabbits. The bioavailability of insulin lispro via the nasal route using a W/O microemulsion was found to reach 21.5% relative to subcutaneous administration, whereas the use of an inverse microemulsion as well as a plain solution yielded less than 1% bioavailability. The profile of plasma glucose levels obtained after nasal spray application of the microemulsion (1 IU/kg lispro) was similar to the subcutaneous profile of 0.5 IU/kg at the first 90 min after application and resulted in a 30-40% drop in glucose levels. The microemulsion system was characterized by DLS. TEM, viscosity measurements, and by construction of pseudo-ternary phase diagram. The average droplet size of an insulin-unloaded and insulin-loaded microemulsions containing 20% aqueous phase (surfactants-to-oil ratio = 87:13) was 2 nm and 2.26 nm in diameter, respectively. In addition, the effect of the microemulsion on FITC-labeled insulin permeation was examined across the porcine nasal mucosa in vitro. The permeability coefficient of FITC-insulin via the microemulsion was 0.210 +/- 0.048 cm/h with a lag time of 10.9 +/- 6.5 min, whereas the permeability coefficient from a plain solution was 0.082 +/- 0.043 cm/h with a lag time of 36.3 +/- 10.1 min. In view of the absorption differences of insulin between 20%, 50% water-containing microemulsions and an aqueous solution obtained in vitro and in vivo, it has been concluded that the acceleration in the intramucosal transport process is the result of encapsulating insulin within the nano-droplet clusters of a W/O microemulsion, while the microemulsion ingredients seems to have no direct role. (C) 2010 Elsevier B.V. All rights reserved.