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Solid Lipid Nanoparticles SLNs for Intracellular Targeting Applications
Published on: November 17, 2015
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Lipid-based nanoparticles: Enhanced cellular uptake via surface thiolation
Patrick Knoll1, Giuseppe Francesco Racaniello2, Valentino Laquintana2
1Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
International Journal of Pharmaceutics
|March 2, 2023
Summary
Thiolated nanostructured lipid carriers (NLCs) with short PEG chains significantly enhance cellular uptake and paracellular permeation. Surface thiol groups on NLCs improve these properties, offering potential for drug delivery applications.
Area of Science:
- Nanotechnology
- Materials Science
- Biomedical Engineering
Background:
- Nanostructured lipid carriers (NLCs) are promising drug delivery systems.
- Surface modification of NLCs can influence their biological interactions.
- Thiolation of NLCs is explored to enhance cellular uptake and permeability.
Purpose of the Study:
- To evaluate the uptake mechanisms of thiolated and non-thiolated NLCs.
- To assess the impact of PEG chain length and thiolation on NLC properties.
- To investigate the influence of NLCs on Caco-2 cell interactions and permeability.
Main Methods:
- Synthesis and characterization of NLCs with varying PEG chain lengths and thiolation.
- Evaluation of NLCs' physical properties (size, PDI, zeta potential, stability).
- In vitro studies on Caco-2 cells, including cytotoxicity, adhesion, internalization, and paracellular permeability assays.
- Cellular uptake studies using endocytosis inhibitors, reducing, and oxidizing agents.
Main Results:
- NLCs exhibited good physical stability and negative zeta potential.
- Thiolated NLCs with short PEG chains (NLCs-PEG10-SH) showed significantly higher cellular uptake (9.5-fold) and increased lucifer yellow permeation (2-fold) compared to non-thiolated counterparts.
- Cellular uptake was primarily mediated by clathrin-dependent endocytosis, with additional pathways (caveolae-dependent, independent) for thiolated NLCs.
- Thiol-dependent uptake mechanisms were identified for thiolated NLCs.
Conclusions:
- Surface thiolation of NLCs, particularly with short PEG chains, substantially enhances cellular uptake and paracellular permeation.
- The findings suggest that thiolated NLCs are a viable strategy for improving drug delivery efficiency.
- Further research into thiol-dependent mechanisms can optimize NLC-based therapeutic strategies.
