Agomelatine (AGM) is a new antidepressant drug with a novel mechanism of action and fewer side effects compared with older antidepressants. AGM is a melatonin receptor (MT1 and MT2) agonist and 5-hydroxytryptamine receptor (5-HT2C) antagonist. In the present study, the enhancement of the oral bioavailability of AGM was formulated and loaded into nanostructured lipid carriers (NLCs), using ultrasonication method. In vitro and ex vivo drug release was performed using a dialysis bag and rat duodenum, respectively. Our pharmacodynamic study showed that AGM–NLCs are more efficacious than a pure drug and marketed product, and confocal microscopy revealed lymphatic uptake of AGM–NLCs. The present study concluded that the NLCs enhanced the oral bioavailability of AGM (6.5-fold) by avoiding its first-pass metabolism by way of lymphatic uptake.

Introduction

Agomelatine (AGM) is a new antidepressant drug with a novel mechanism of action and fewer side effects compared with older antidepressants, such as selective serotonin reuptake inhibitors and tricyclic antidepressants. AGM is a melatonin receptor (MT1 and MT2) agonist and 5-hydroxytryptamine receptor (5-HT2C) antagonist. It undergoes extensive first-pass metabolism showing poor oral bioavailability (<5%). The purpose of this study was to develop a delivery system capable of improving its oral bioavailability. It was hypothesized that by formulating AGM loaded into nanostructured lipid carriers (NLCs) and targeting Peyer’s patch, the oral bioavailability could be increased and hence the therapeutic effect also increased. It can also be effective long term by having a controlled release of the drug from NLCs. NLCs are second-generation lipidic nanoparticles, which have gained the interest of scientists for the oral delivery of drugs. By developing a system like NLCs, one can enhance the solubility, and as the system is lipidic in nature and nano size, NLCs can directly and easily get absorbed by the M cells of Peyer’s patches. It can also avoid first pass metabolism due to their nano size.

Int J Nanomedicine. 2018; 13: 35–38.

Published online 2018 Mar 15. doi:  10.2147/IJN.S124703