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Polymeric nanoparticles as a platform for nose-to-brain delivery
Marie Bolon1, Morgane Marie1, Simon Megy1
1UMR 5305: Laboratoire de Biologie Tissulaire et d'Ingénierie thérapeutique, Institut de Biologie et Chimie des Protéines, CNRS/Université Claude Bernard Lyon 1, CEDEX 07, 69367, Lyon, France. sophie.richard@univ-lyon1.fr.
Journal of Materials Chemistry. B
|August 29, 2025
Summary
Polymeric nanoparticles offer a non-invasive nose-to-brain delivery (NtBD) method for brain disorders. NP-PLA-P188 nanoparticles show promise for safe and effective drug delivery to the brain.
Area of Science:
- Nanotechnology
- Neuroscience
- Drug Delivery
Background:
- Nose-to-brain delivery (NtBD) is a promising non-invasive strategy to bypass the blood-brain barrier for treating brain disorders.
- Polymeric nanoparticles (NPs) offer potential for targeted drug delivery.
- Poloxamers can enhance nanoparticle properties for biological applications.
Purpose of the Study:
- To develop and characterize polylactic acid (PLA) and poloxamer (P188, P407) based nanoparticles for nose-to-brain delivery.
- To evaluate the structural integrity, colloidal stability, biocompatibility, and brain targeting efficiency of the developed NPs.
- To identify an optimal nanoparticle formulation for effective and safe NtBD.
Main Methods:
- Synthesis of polymeric nanoparticles (NPs) using one-step or two-step nanoprecipitation.
- Characterization of NPs including size, charge, and structural organization via dissipative particle dynamics simulations.
- Assessment of colloidal stability in artificial mucus and cerebrospinal fluid.
- In vitro cytotoxicity and cellular uptake studies using human nasal epithelial and neuronal cells.
- In vivo evaluation of brain targeting using fluorescence imaging and immunostaining.
Main Results:
- Homogeneous, negatively charged NPs (approx. 110 nm) were successfully synthesized.
- Poloxamer modification enhanced NP colloidal stability in simulated biological fluids.
- NPs exhibited no cytotoxicity and were taken up by both epithelial and neuronal cells in vitro.
- In vivo studies confirmed NP presence in the olfactory bulb within one hour post-administration.
- NP-PLA-P188 formulation demonstrated significant potential for brain delivery.
Conclusions:
- Polymeric nanoparticles based on PLA and poloxamers are suitable for nose-to-brain delivery.
- Poloxamer-modified NPs show improved stability and biocompatibility.
- The NP-PLA-P188 formulation is a promising candidate for non-invasive drug delivery to the brain for neurological diseases.
