Date of Award


Document Type


Degree Name

Philosophy (Ph.D)


Pharmaceutical Sciences

First Advisor

Jun Shao

Second Advisor

Sabesan Yoganathan

Third Advisor

Louis Trombetta


This study aimed to investigate the permeation enhancing property and safety of self-emulsified nanoemulsion (SEN) and use these findings to enhance insulin absorption through the nasal route.

The first part of the project was to identify the factors affecting cytotoxicity and permeation enhancement of SEN on Madin-Darby Canine Kidney (MDCK) cells, a widely used paracellular model. Twenty-six fatty acid esters (FAEs) commonly used in SEN were investigated. Among the FAEs (mono-, di-, and triesters), fatty acid monoesters (FAME) are the main excipient causing cytotoxicity and opening tight junction. The cytotoxicity of FAME in SEN was reduced with the presence of triglycerides, the increase in droplet size, and the higher intermolecular interaction within the lipid droplets.

Then, the SENs consisted of various FAMEs, medium-chain triglyceride and Kolliphor®RH40 (1:1:2) were evaluated for their capability to enhance insulin across human airway epithelium cell (Calu-3) monolayer. The SENs containing medium-chain monoglyceride, G8/10MD (C8/C10 mono/diglycerides) showed the greatest permeability enhancement on insulin across the Calu-3 monolayer. The opening of the tight junction was reversible. Also, the SEN containing G8/10MD (SEN-G8/10MD) could prevent the fibril formation of insulin.

Therefore, SEN-G8/10MD was selected for the ex vivo and in vivo studies. SEN-G8/10MD (0.8-30%) had droplet size of 31±9 nm, polydispersity index of 0.065±0.031 and zeta potential of -1.86±0.74 mV. The permeability of insulin across the ex vivo bovine nasal mucosa was significantly (p<0.05) increased by SEN-G8/10MD at 20% of the preconcentrate with a minimum nasociliotoxicity observed. In vivo study in streptozotocin-induced diabetic rats showed that as compared to subcutaneous injection, the relative pharmacodynamics availability achieved by SEN-G8/10MD at 20%, 10%, and 5% of the preconcentrate were 79.5%, 58.4% and 42.0%, respectively, significantly higher (p<0.05) than the 1.4% by the solution form. The three SENs also achieved the relative bioavailability of 37.9%, 19.3% and 8.8%, respectively, and the first two were significantly (p<0.05) higher than the 4.0% by the solution form. The SENs did not cause noticeable toxicity on the rats’ nasal epithelium.

In conclusion, the SEN containing G8/10MD has a potential to deliver insulin across the nasal route.