Abstract
The overall objective of this research was to evaluate the potential of Melanotan-I (MT-I) for oral delivery in humans. An in vitro cell monolayer model (Caco-2) was used to screen the effect of certain absorption enhancers on the transport of MT-I. The enhancers used were dimethyl-βcyclodextrin (DMβCD), sodium tauro-dihydrofusidate (STDHF), and aprotinin, a protease inhibitor. In addition, the effect of the most promising enhancers on the bioavailability of MT-I was deter-mined using an in situ closed loop rat model. In the Caco-2 monolayer model, coadministration of MT-I with aprotinin produced a 2.4-fold increase in the trans-port of MT-I. No significant enhancement was seen with either DMβCD or STDHF. Thus, inhibition of degradation of MT-I by proteases appears to be the most promising approach for delivering MT-I via the oral route. Finally, an attempt was made to compare the transport data from the Caco-2 model to bioavailability data in the rat model. The trends observed for both models were comparable and the data from the rat studies were in good agreement with the results obtained with the Caco-2 model.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 49-55 |
| Number of pages | 7 |
| Journal | Drug Delivery |
| Volume | 2 |
| Issue number | 1 |
| DOIs | |
| State | Published - 1995 |
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ASJC Scopus subject areas
- Pharmaceutical Science
- Pharmacology
Cite this
Absorption enhancement of melanotan-l : Comparison of the caco-2 and rat in situ models. / Surendran, Narayanan; Ugwu, Sydney O.; Nguyen, Linh D.; Sterling, Eric J.; Dorr, Robert T; Blanchard, James.
In: Drug Delivery, Vol. 2, No. 1, 1995, p. 49-55.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Absorption enhancement of melanotan-l
T2 - Comparison of the caco-2 and rat in situ models
AU - Surendran, Narayanan
AU - Ugwu, Sydney O.
AU - Nguyen, Linh D.
AU - Sterling, Eric J.
AU - Dorr, Robert T
AU - Blanchard, James
PY - 1995
Y1 - 1995
N2 - The overall objective of this research was to evaluate the potential of Melanotan-I (MT-I) for oral delivery in humans. An in vitro cell monolayer model (Caco-2) was used to screen the effect of certain absorption enhancers on the transport of MT-I. The enhancers used were dimethyl-βcyclodextrin (DMβCD), sodium tauro-dihydrofusidate (STDHF), and aprotinin, a protease inhibitor. In addition, the effect of the most promising enhancers on the bioavailability of MT-I was deter-mined using an in situ closed loop rat model. In the Caco-2 monolayer model, coadministration of MT-I with aprotinin produced a 2.4-fold increase in the trans-port of MT-I. No significant enhancement was seen with either DMβCD or STDHF. Thus, inhibition of degradation of MT-I by proteases appears to be the most promising approach for delivering MT-I via the oral route. Finally, an attempt was made to compare the transport data from the Caco-2 model to bioavailability data in the rat model. The trends observed for both models were comparable and the data from the rat studies were in good agreement with the results obtained with the Caco-2 model.
AB - The overall objective of this research was to evaluate the potential of Melanotan-I (MT-I) for oral delivery in humans. An in vitro cell monolayer model (Caco-2) was used to screen the effect of certain absorption enhancers on the transport of MT-I. The enhancers used were dimethyl-βcyclodextrin (DMβCD), sodium tauro-dihydrofusidate (STDHF), and aprotinin, a protease inhibitor. In addition, the effect of the most promising enhancers on the bioavailability of MT-I was deter-mined using an in situ closed loop rat model. In the Caco-2 monolayer model, coadministration of MT-I with aprotinin produced a 2.4-fold increase in the trans-port of MT-I. No significant enhancement was seen with either DMβCD or STDHF. Thus, inhibition of degradation of MT-I by proteases appears to be the most promising approach for delivering MT-I via the oral route. Finally, an attempt was made to compare the transport data from the Caco-2 model to bioavailability data in the rat model. The trends observed for both models were comparable and the data from the rat studies were in good agreement with the results obtained with the Caco-2 model.
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UR - http://www.scopus.com/inward/citedby.url?scp=0028914940&partnerID=8YFLogxK
U2 - 10.3109/10717549509031351
DO - 10.3109/10717549509031351
M3 - Article
VL - 2
SP - 49
EP - 55
JO - Drug Delivery
JF - Drug Delivery
SN - 1071-7544
IS - 1
ER -