PLGA-FUNCTIONALIZED NANOPARTICLES FOR INTRANASAL DELIVERY OF NEUROPROTECTIVE CUES: AN ALTERNATIVE STRATEGY FOR TARGETED NEURAL SUPPORT

Conventional cancer therapies, while significantly improving patient survival, are frequently associated with long-term cognitive side effects. Up to 70% of cancer survivors experience chemobrain, characterized by memory deficits, reduced attention, and mental fog, often accompanied by depressive symptoms. These alterations arise from the loss of neural stem cells (NSCs) induced by the limited specificity of anticancer treatments, together with the low regenerative capacity of the postnatal brain.
In this study, we present a biodegradable nanoparticle platform for intranasal administration designed to selectively support neural progenitor cell (NPC) viability during aggressive oncological therapies. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were produced via nanoprecipitation and functionalized to enhance stability and targeting potential. Physicochemical and morphological characterization was performed using dynamic light scattering, atomic force microscopy, and transmission electron microscopy. Biocompatibility and functional integrity were evaluated in primary cortical and hippocampal cultures using MTT viability assays and electrophysiological recordings on Micro-Electrode Arrays. To enable drug delivery, epidermal growth factor (EGF) and fibroblast growth factor (FGF) were tested to selectively promote NPC proliferation without stimulating tumor growth. Encapsulation efficiency and release kinetics were then assessed.
The results demonstrate the formation of stable and fully biocompatible nanoparticles, with cell viability exceeding 80% and no detectable alterations in neuronal activity. Combined delivery of EGF and FGF was identified as the most effective strategy to selectively enhance NPC proliferation while exerting minimal effects on neuroblastoma cells.
Overall, this nanoparticle-based strategy targeting the central nervous system represents a promising approach to mitigate therapy-induced neurotoxicity and preserve neurogenic niches.