Targeted Delivery of mGluR1 Ligand RMGOH via Lipid Nanoparticles: A Novel Approach for Enhancing CNS Drug Accessibility

Abstract

Delivering pharmaceuticals to the brain is challenging due to the blood-brain barrier (BBB), which limits unwanted substance entry. This study focuses on developing effective targeting strategies for central nervous system (CNS) diseases. The selective mGluR1 receptor ligand, RMGOH, was identified using computational tools like ADMET analysis, molecular docking, and molecular dynamics simulations. RMGOH demonstrated promising binding affinity with a Glide Score of -4.13 kJ/mol and favorable pharmacokinetic properties for BBB and CNS permeability. The synthesis of RMGOH nanolipid was conducted with DSPC cationic lipids, followed by in-vitro and in-vivo studies. The nanoparticles exhibited an average size of 179 nm and controlled drug release over 72 hours. Hemolysis tests indicated RMGOH's safety for in-vivo applications. The compound achieved over 95% radiolabelling efficiency with 99mTc, and biodistribution studies showed significant brain uptake. RMGOH-LNs are promising for evaluating mGluR1 outcomes in specific brain regions.