Abstract
Copper (Cu(2 +)) dysregulation, often stemming from ATP7B gene mutations, exacerbates neurological disorders like Huntington's, Alzheimer's, and Parkinson's diseases. Monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA) shows promise in mitigating Cu(2+) induced neurotoxicity by chelating intracellular Cu(2+) ions, reducing oxidative stress, and restoring antioxidant enzyme function. However, challenges such as poor bioavailability hinder its therapeutic efficacy. Nano-delivery systems offer a solution by improving MiADMSA's solubility, stability, and targeted delivery, potentially minimizing off-target effects. In this study, MiADMSA was loaded into a polymer conjugated with lipoic acid (LA) and human serum albumin (HSA) using a coacervation crosslinking method. The prepared nanoparticles were optimized using a Box-Behnken design. Evaluation in SH-SY5Y cells revealed promising neuroprotective effects against Cu(2+) induced neurotoxicity, highlighting the potential of MiADMSA-loaded nanocarriers as a therapeutic strategy for neurodegenerative diseases associated with metal dysregulation.