Comparative study of the structural and physicochemical properties of two food derived antihypertensive tri-peptides, Isoleucine-Proline-Proline and Leucine-Lysine-Proline encapsulated into a chitosan based nanoparticle system

Food derived tri-peptides; Leucine-Lysine-Proline (LKP) and Isoleucine-Proline-Proline (IPP) are angiotensin converting enzyme inhibitors and may have potential to alleviate hypertension. The aim of this work was to understand the interactions of IPP and LKP when formulated into a chitosan nanoparticle (NP) to help improve permeation. Our findings indicate different mean inhibitory concentrations (LKP: 0.36 ± 0.01 μM and IPP: 3.1 ± 0.6 μM) and encapsulation efficiencies at different ratios of chitosan: tripolyphosphate (LKP NPs: 65% at 6:1 and IPP NPs: 43% at 4:1). Molecular modelling and circular dichroism showed different stable amino side-chain-specific conformations for each peptide. IPP showed more steric hindrances to intra-chain rotations, resulting in an unordered peptide structure, whereas LKP showed more flexibility associated with a (disordered) β-strand-like conformer. In-vitro release kinetics showed a slower release for LKP NPs in acidic pH compared to IPP NPs. In conclusion, LKP NPs were found to have better binding compatibility with chitosan.