Absorption enhancement of melanotan-l: Comparison of the caco-2 and rat in situ models

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.