MSN Templated with L-Dopa Amide Derivatives Outperforms the Efficiency of Free-L-Dopa in Reducing Parkinson’s Behavioral Dysfunction in Mice

In this study, we developed mesoporous silica nanoparticles (MSNs) templated with L-dopa amide derivatives, specifically designed as a drug-structure-directing agent (DSDA). This novel templating approach improves L-dopa loading capacity and enhances controlled-release performance. Two MSN formulations were selected for in vivo evaluation in a murine model of PD induced by unilateral injection of 6-hydroxydopamine (6-OHDA) in the striatum.

Results: In vitro studies demonstrated that L-dopa derivatives-loaded MSNs lead to a controlled and sustained release of L-dopa DSDA and in vivo assays corroborated this hypothesis. A single intraperitoneal dose of L-dopa-loaded MSNs was able to reduce the spontaneous rotational behavior observed in 6-OHDA damaged mice and outdid free-L-dopa. Conclusion: This novel strategy may represent a promising alternative to conventional treatment, reducing dose frequency and hencem minimizing L-dopa side effects.

The results herein emphasize the potential of MSN-based drug delivery systems for PD, providing a basis for future translational research of nanotechnology-based formulations for neurodegenerative disorders.