Solid and Nanostructured Lipid Carriers for Plant-Derived Neuroprotective Agents: Advances and Future Perspectives

Abstract

Neurodegenerative disorders, particularly Alzheimer's disease (AD) and Parkinson's disease (PD), continue to pose a substantial therapeutic challenge, largely due to progressive neuronal degeneration and the limited effectiveness of currently available treatments. Plant-derived bioactive compounds-including polyphenols, alkaloids, terpenoids, and flavonoids-have shown notable neuroprotective properties. However, their clinical use remains constrained by low bioavailability and limited ability to cross the blood-brain barrier (BBB). Lipid-based nanocarrier systems, especially solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), have emerged as promising alternatives for improving delivery efficiency. This review evaluates recent advances in SLN and NLC formulations developed for phytochemical delivery in neurodegenerative conditions, focusing on formulation approaches, production methods, and the physicochemical factors that govern system performance. Preclinical findings consistently indicate enhanced solubility, improved stability, and more effective brain targeting with these systems. Even so, several challenges continue to impede their clinical translation. In particular, issues related to formulation reproducibility, scalability of production, and long-term safety remain unresolved. Alternative administration routes such as intranasal delivery offer a potential strategy to bypass the BBB, although their practical feasibility still requires further confirmation. SLN- and NLC-based systems offer a promising approach, although their clinical development is still ongoing. Future efforts should focus on establishing standardized formulation protocols, conducting rigorous in vivo studies, and ensuring alignment with regulatory requirements to facilitate successful clinical translation.