Date of Award


Document Type


Degree Name

Philosophy (Ph.D)


Pharmaceutical Sciences

First Advisor

Jun Shao

Second Advisor

Zhesheng Chen

Third Advisor

Senshang Lin


The present study aimed to explore the biodistribution of O/W nanoemulsions (NE) upon intravenous administration. Three NEs were prepared with distinctive droplet sizes: SE (29 ± 1 nm), ME (214 ± 2 nm) and LE (883 ± 16 nm) without overlapping of the size distribution. Kolliphor® HS15 was used as the only surfactant for these three NEs, so that their droplets had similar surface structure. The NEs droplet size was stable under room temperature for minimum 3 days in phosphate buffer saline (PBS) and in mice plasma in vitro for 4-hour at 37°C. A lipophilic fluorescent dye, 1, 1’-dioctadecyl-3, 3, 3’, 3’-tetramethylindocarbocyanine perchlorate (DiI) was selected as the probe and loaded in the SE, ME and LE (designated thereafter as DSE, DME and DLE, respectively). A fluorometry for DiI was established with a linear range of 1.0-1000 ng/mL.

The processing procedure and assay method for biological samples were developed. DiI extraction efficiency was 74.6-93.4%, depending on the tissues. For the biodistribution study, tumor-bearing mice received intravenous injection of DiI (2-5 mg/kg) in free solution (DS) or in the NEs via tail vein. The mice were sacrificed at sampling time points and the biological samples were assayed for DiI concentrations. DS manifested early tissues peak concentration (apparent Tmaxs at 0.5 h) followed by rapid decline, with tissue recovery mainly from the liver, spleen and lungs. DSE had a comparable plasma profile as DS but lower concentrations in the spleen and lungs as compared to the corresponding tissue profiles followed by the administration of DS. DME showed a sustained plasma circulation and a long-term non-specific higher tissue uptake with significant accumulation in the heart, lung, liver and spleen. DLE displayed a favorable accumulation in the RES organs including the lung, spleen, and liver. In conclusion, the present study demonstrates that O/W NE exhibits altered biodistribution upon intravenous administration. And these features may be utilized as a targeted drug delivery and drug redisposition strategy.