Combined approaches for targeting the dipeptidyl peptidase-IV (DPP-IV) enzyme: development of hypoglycaemic chemometric model, nanoformulation and in vitro studies using natural compound(s)

Dipeptidyl peptidase-IV (DPP-IV) is a crucial enzyme in metabolism management. Several natural compounds have been identified for the management of diabetes by inhibiting the DPP-IV enzyme, but they either express inadequate inhibition or lack a mechanistic approach. In the present studies, the chemometric model (MLR) was developed using natural compounds, and the compound with the most influential descriptor was selected for the preparation of microemulsion to counter the pharmaceutical challenges. The chemometric model resulted in caffeic acid (CA). The developed microemulsion (CAME) was characterised for globule size, zeta potential and polydispersity index with the respective values of 87.8 nm, 0.13 mV and 0.25. The spherical shape of MEs was confirmed by transmission electron microscopy (TEM). The drug released study for the prepared formulation was nearly 12% of CA in 0.1 N HCl for 2 h, 22.1% at pH 6.8 in the next 4 h. In pharmacokinetic studies, the bioavailability of CAME was increased fourfold compared to plain CA. The IC50 was 81.4 and 36.3 μM, respectively, for CA and CAME against the DPP-IV enzyme. Thus, these novel MEs could be promising in targeting the membrane-anchored DPP-IV enzyme by inhibiting the enzyme and enhanced oral bioavailability, warranting future in vivo pharmacodynamic studies to establish its therapeutic efficacy.