The effect of the shape of nanocarriers on their transmembrane across Caco-2 cell monolayer / 药学学报

ABSTRACT

Cerasomes with different shapes were constructed to investigate the effect of the nanocarriers' shape on the cellular uptake and transmembrane capacity. Cerasome-forming lipid (CFL) was synthesized via halogenation, nucleophilic addition and acylation reaction and detected by mass spectrometry and nuclear magnetic resonance spectroscopy. CFL and short chain 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) were employed to prepare organic-inorganic hybrid bicelles in discal shapes (nanodisc) by the thin-film hydration method, and CFL was also used to prepare spherical cerasomes (nanosphere). The particle size and zeta potential of nanocarriers were measured by dynamic light scattering analysis, and the morphology was observed by transmission electron microscopy. With human colon cancer cell line Caco-2 as the model, the effect of the shape of nanocarriers on cellular uptake and transmembrane capacity was investigated qualitatively by confocal laser scanning microscope (CLSM), and the transmembrane capacity was analyzed quantitatively by high performance liquid chromatography (HPLC). The results showed that nanosphere and nanodisc had similar particle diameters around 110 nm and similar zeta potential around -25 mV, with regular morphology under transmission electron microscope. The cellular uptake rate of nanodisc was significantly higher than that of nanosphere in 20 minutes. Further research on Caco-2 cell monolayer demonstrated that nanodisc with faster uptake had less accumulation in the monolayer, which means it had a higher transmembrane rate on Caco-2 cell monolayer and the transmembrane capacity of the nanodisc was better than that of nanosphere within 2 h. These results suggest that rational design of the shape of nanocarriers is expected to regulate nano-bio interactions, promote the transmembrane transport of nanocarriers, and improve the drug absorption.