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  • Title: Oral drug delivery: Influence of mucus on cellular interactions and uptake of lipid-based nanocarriers in Caco-2 cells.
    Author: Veider F, Knoll P, Jörgensen AM, Stengel D, Bernkop-Schnürch A.
    Journal: Acta Biomater; 2023 Sep 01; 167():416-424. PubMed ID: 37311506.
    Abstract:
    This study aimed to investigate the impact of the mucus gel barrier on intestinal mucosal uptake of lipid-based nanocarriers (NCs). Zwitterionic- (ZW), polyglycerol- (PG) and polyethylene glycol- (PEG) surfactant-based o/w nanoemulsions were developed. NCs were assessed regarding their size and zeta potential, stability in biorelevant media and mucus, mucus permeation behavior, cellular interactions and uptake by Caco-2 cells with and without mucus and by a Caco-2/HT29-MTX co-culture. All NCs were in the size range of 178 - 204 nm and exhibited a zeta potential between -4.2 and +1.2 mV. ZW- and PG-NCs demonstrated mucus permeating properties comparable to PEG-NCs. In contrast, ZW- and PG-NCs showed high cellular uptake, whereas limited cellular uptake was observed in case of PEG-NCs. Furthermore, mucus on Caco-2 cells as well as the mucus secreting co-culture had a significant impact on the cellular uptake of all tested NCs. According to these results, ZW- and PG-NCs are advantageous to overcome the mucus and epithelial barrier of the intestinal mucosa. STATEMENT OF SIGNIFICANCE: Within this study the impact of mucus on cellular uptake of lipid-based nanocarriers (NCs) with different surface decorations was investigated. The potential of NCs with zwitterionic-, polyglycerol- and polyethylene glycol-surfactants on their surface to overcome the mucus and epithelial barrier was evaluated. Zwitterionic- and polyglycerol-NCs showed mucus permeating properties similar to PEG-NCs. In contrast, zwitterionic- and polyglycerol-NCs substantially outperformed PEG-NCs in their cellular uptake properties. According to these findings, zwitterionic- and polyglycerol-NCs have the potential to overcome both the mucus and epithelial barrier of the mucosa.
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