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Colloidal stability as a determinant of nanoparticle behavior in the brain
Chad Curtis1, Dorsa Toghani2, Ben Wong3
1Department of Chemical Engineering, University of Washington, Seattle, WA, 98195, United States.
Colloids and Surfaces. B, Biointerfaces
|July 10, 2018
Summary
Poly(ethylene glycol)-coated nanoparticles (NPs) demonstrate superior stability and diffusion in brain fluid conditions compared to carboxyl-coated NPs. This highlights the importance of steric stabilization for effective nanoparticle drug delivery to the brain.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Neuroscience
Background:
- Drug delivery to the brain is hindered by the blood-brain barrier (BBB) and complex brain microenvironment.
- Nanoparticles offer tunable properties for enhanced brain drug delivery, but their interactions within the brain are not fully understood.
- Cerebrospinal fluid (CSF) composition, including ion concentration and pH, can significantly impact nanoparticle behavior.
Purpose of the Study:
- To systematically investigate how CSF conditions affect nanoparticle behavior, specifically aggregation kinetics, colloidal stability, and diffusion.
- To compare the performance of poly(ethylene glycol)-coated (PS-PEG) and carboxyl-coated (PS-COOH) polystyrene nanoparticles (NPs) under brain-relevant conditions.
- To determine the role of surface coating and steric stabilization in maintaining nanoparticle functionality for brain drug delivery.
Main Methods:
- Synthesized and characterized PS-PEG and PS-COOH nanoparticles with varying sizes, charges, and coatings.
- Evaluated nanoparticle aggregation kinetics and colloidal stability across a range of CSF ion concentrations, compositions, and pH levels.
- Assessed nanoparticle diffusive capability using agarose gels and organotypic brain tissue slice models.
Main Results:
- Small changes in calcium concentration and pH significantly destabilized nanoparticles in CSF.
- PS-PEG nanoparticles exhibited greater colloidal stability and remained stable under a wider range of conditions compared to PS-COOH nanoparticles.
- PS-PEG nanoparticles demonstrated enhanced diffusion capabilities in both in vitro agarose gel models and ex vivo brain tissue models.
Conclusions:
- Steric stabilization, provided by PEG coatings, is crucial for maintaining nanoparticle colloidal stability in the complex brain microenvironment.
- Colloidal stability directly correlates with increased nanoparticle diffusive capability, essential for effective brain drug delivery.
- Understanding and controlling nanoparticle-CSF interactions is vital for designing successful nanoparticle-based therapeutics for neurological diseases.
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