INSULIN ORAL DELIVERY: SYNERGISTIC EFFECT OF AZONE, BACITRACIN, AND GOLD NANOPARTICLE
SEUNG MIN OH
Poverty Research Laboratory, 111 Charlotte Place #100/ Englewood Cliffs, NJ 07632, USA.
JIHUN HAN
Poverty Research Laboratory, 111 Charlotte Place #100/ Englewood Cliffs, NJ 07632, USA.
YU JIN CHO
Poverty Research Laboratory, 111 Charlotte Place #100/ Englewood Cliffs, NJ 07632, USA.
ANTHONY W. BAE
Poverty Research Laboratory, 111 Charlotte Place #100/ Englewood Cliffs, NJ 07632, USA.
GI WON SUNG
Poverty Research Laboratory, 111 Charlotte Place #100/ Englewood Cliffs, NJ 07632, USA.
HAE SEOK YOON
Poverty Research Laboratory, 111 Charlotte Place #100/ Englewood Cliffs, NJ 07632, USA
KAREN JANG
Poverty Research Laboratory, 111 Charlotte Place #100/ Englewood Cliffs, NJ 07632, USA.
ANDREW HWANG
Poverty Research Laboratory, 111 Charlotte Place #100/ Englewood Cliffs, NJ 07632, USA.
SERIN AHN
Poverty Research Laboratory, 111 Charlotte Place #100/ Englewood Cliffs, NJ 07632, USA.
TAEHYUK KIM
Poverty Research Laboratory, 111 Charlotte Place #100/ Englewood Cliffs, NJ 07632, USA.
YOUNGIL CHUNG
Poverty Research Laboratory, 111 Charlotte Place #100/ Englewood Cliffs, NJ 07632, USA.
ESTHER NAM
Poverty Research Laboratory, 111 Charlotte Place #100/ Englewood Cliffs, NJ 07632, USA.
JONGBIN LEE *
Poverty Research Laboratory, 111 Charlotte Place #100/ Englewood Cliffs, NJ 07632, USA.
*Author to whom correspondence should be addressed.
Abstract
Oral insulin follows the physiology of endogenous insulin secreted in pancreas. Intestinal absorption of oral insulin assist its uptake into blood stream and subsequently into the liver at the concentration of blood glucose reduction via the portal vein. Still, various transport barriers dwarf the insulin bio availabilty when administered orally. Therefore, systematic approach of oral insulin formulation has been required. To overcome these transport barriers, an improved formulation of insulin with various excipients was investigated, while being adminitered orally using gradual combinations of the gold nanoparticle, azone, and bacitracin in a rodent experimental model. The objective of the study was to examine the enhancing profiles of insulin uptake while adding the excipients in a step-wise manner.
Experimental results with pharmacodynamic parameters demonstrated that there existed a synergistic effect additively when evaluated in BG change% and AUC. The maximal BG% decrease and AUC with respect to adding ingredients showed a high linearity with the step-wise addition of each composition (R2>0.90). The result led us to draw a conclusion that the addition of the excipients into the oral insulin formulations induced a synergistic increase in BG drop.
Keywords: Oral insulin, alternate delivery, protein and peptide drugs, pharmacodynamic analysis, penetration promoters, enzyme inhibitors