Innovative glycochenodeoxycholic Acid-Acrylamide Nanopolymer carriers: Regulating upper critical solution temperature on neurorehabilitation

Abstract

Neurorehabilitation focuses on restoring function in patients with central and peripheral nervous system disorders, yet effective therapeutic options remain scarce. This study introduces a novel nanocopolymer, CaCO₃-PAAm-GDCA, synthesized through reversible addition-fragmentation chain transfer polymerization of glycodeoxycholic acid, acrylamide, and CaCO₃. This nanocopolymer exhibits a sharp and reversible insoluble-to-soluble transition in water at a temperature related to its upper critical solution temperature (UCST), which can be finely adjusted to a practical range around 37 °C, suitable for biomedical applications. The addition of β-cyclodextrin (β-CD) modulates this transition temperature by forming host-guest complexes, further enhancing the copolymer’s adaptability. When loaded with compound 1, the resulting CaCO₃-PAAm-GDCA@1 significantly promoted the proliferation of damaged neuronal HT22 cells and inhibited ferroptosis through the modulation of Nrf2 and GPX4 pathways. This study provides a strong foundation for the development of neuroprotective drugs, highlighting the potential of tailored nanocopolymers in advanced neurorehabilitation therapies.