L-ornithine liposomal nanoparticles as competitive inhibitor against Δ1-pyrroline-5-carboxylate dehydrogenase: Kinetic perspective hepatic encephalopathy therapy.

Hepatic encephalopathy (HE) is a life-threatening neuropsychiatric disorder. This study aimed to synthesize L-ornithine liposomal nanoparticles and evaluate their inhibitory degree against Δ1pyrroline-5-carboxylate dehydrogenase (Δ1P5CDH) for HE treatment. To verify the probable binding affinities for L-ornithine and LOLA against Δ1P5CDH, molecular docking in-silico studies were conducted, and pharmacokinetic features, such as ADMET and Pro-tox-3.0 platforms, were carried out. L-ornithine liposomal nanoparticles were synthesized and characterized using EE%, DL%, FTIR, TEM, SEM, EDX, XRD, zeta potential, and sizer. The in-vitro MTT assay on the WI-38 normal cell line was investigated. The in-vivo enzymatic inhibition (Ki) was determined using the Lineweaver-Burk blot. The results elucidated that the liposomal nanoparticles of L-ornithine improved their spherical shape, size, and stability by the structural and spectral analyses. Further, the docking calculations showed that L-ornithine has the top binding energy (-6.9854 kcal/mol) with the Δ1P5CDH protein binding pocket. Moreover, the ADMET score and Pro-tox-3.0 reported excellent accessibility with minimal toxicity, which was confirmed by in-vitro studies on the normal WI-38 cell line, as L-ornithine, LOLA, and Nano L-ornithine have IC50 equal to 108.9 ± 2.2, 95.42 ± 1.54, and 128.8 ± 2.8 μg/mL, respectively. In addition, L-ornithine liposomal nanoparticles observed a more competitive inhibitor degree than L-ornithine and LOLA towards the target Δ1P5CDH, which is a potential therapeutic enzyme for HE treatment. From our findings, we further clarified that the L-ornithine liposomal nanoparticles could be a potential therapeutic candidate against HE via Δ1P5CDH inhibition.