Date of Award


Document Type


Degree Name

Philosophy (Ph.D)


Pharmaceutical Sciences

First Advisor

Jun Shao

Second Advisor

Sabesan Yoganathan

Third Advisor

Abu Serajuddin


The main objective of this research was to develop an o/w nanoemulsion dosage form of insulin for intranasal delivery where insulin is loaded into the oil phase of the nanoemulsion for enhanced absorption. When loaded into the lipid droplets (oil phase), insulin can be protected from enzymatic degradation, can permeate through the mucus gel barrier in a comparatively efficient manner and can be absorbed through transcellular permeation along with paracellular route. To incorporate lipophilicity to insulin molecule, several complexes of insulin with various amphiphiles were developed to load it into the oil phase. The cytotoxicity of these amphiphiles and the developed nanoemulsions was tested on the human nasal epithelial cells in vitro. An optimized formulation with high loading of insulin and low in vitro cytotoxicity was developed and characterized. To predict the absorption of insulin through nasal membrane in vivo by the nanoemulsion system, the insulin-loaded nanoemulsion along with controls was tested for the transport across human nasal epithelial cell monolayer in vitro. The nanoemulsion significantly (p < 0.01) enhanced the permeation of insulin by three times as compared to the insulin solution. The in vivo absorption of insulin after intranasal delivery of the insulin-loaded nanoemulsion was evaluated in anesthetized rats. The results show that the maximum plasma concentration (Cmax) and the bioavailability (relative to the subcutaneous delivery) of the insulin-loaded nanoemulsion was 255.9 µU/ml and 68 %, respectively, while the intranasal delivery of the insulin solution resulted only 5.8 µU/ml of Cmax and 5% of relative bioavailability. Intranasal delivery of 3.6 IU/kg insulin in nanoemulsion decreased the plasma glucose level remarkably, achieving a maximum reduction of 70%, and the glucose reduction activity lasted for the whole experimental period of 4 h. These results demonstrate that the nanoemulsion significantly enhanced insulin absorption through intranasal delivery, indicating that the developed nanoemulsion system offers a promising approach for intranasal delivery of insulin.