Influence of Physicochemical Properties and PEG Modification of Magnetic Liposomes on Their Interaction with Intestinal Epithelial Caco-2 Cells

Abstract

The present study aimed to investigate the effect of particle size (100, 500 nm), surface charge (cationic, neutral and anionic) and polyethylene glycol (PEG) modification of magnetic liposomes on their interaction with the human intestinal epithelial cell line, Caco-2. The cellular associated amount of all the magnetic liposomes was significantly increased by the presence of a magnetic field. The highest association and internalization into Caco-2 cells was observed with magnetic cationic liposomes. Moreover, small magnetic liposomes were more efficiently associated and taken up into the cells, than large ones. In contrast, PEG modification significantly attenuated the enhancing effect of the magnetic field on the cellular association of magnetic liposomes. We also found that magnetic cationic liposomes had the highest retention properties to Caco-2 cells. Moreover, the retention of large magnetic liposomes to the cells was much longer than that of small ones. In addition, magnetic cationic and neutral liposomes had relatively high stability in Caco-2 cells, whereas magnetic anionic liposomes rapidly degraded. These results indicate that the physicochemical properties and PEG modification of magnetic liposomes greatly influences their intestinal epithelial transport.

Janus microspheres for enhanced enteral drug delivery: Preparation and orientated attachment to a Caco-2 monolayer

“…Although the surface of the Caco-2 monolayer appears to be hydrophobic, it is known that charged particles can become strongly attached. In studies using liposomes (35) and oil droplets (36), it has been demonstrated that cationic particles can attach to Caco-2 monolayers to a greater extent than anionic and neutral particles. The polymeric hemisphere-orientated attachment of the Janus microspheres to Caco-2 monolayers observed in the present study appears to be consistent with the findings of these studies, because these microspheres consist of cationic polymer and neutral hard-fat hemispheres.…”

Enhanced macrophage delivery to the colon using magnetic lipoplexes with a magnetic field

“…Magnetic cationic liposomes were prepared as reported previously (Kono et al., 2017). Magnetic cationic liposomes consisted of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) (Avanti Polar Lipids Inc., Alabaster, AL, USA), 1,2-distearoyl- sn -glycero-3-phosphocholine (DSPC) (Avanti Polar Lipids), and cholesterol (Nacalai Tesque, Kyoto, Japan) at molar ratios of 5:0:5, 4:1:5, 3:2:5, or 2:3:5.…”

“…For the efficient introduction of SPIONs into macrophages, we intended to exploit cationic liposomes, because we have previously prepared cationic liposomes with encapsulated SPIONs (magnetic cationic liposomes) and demonstrated that they underwent cellular uptake in a short time under a magnetic field (Kono et al., 2017). In addition, cationic liposomes can form a complex with plasmid DNA (pDNA) (Masotti et al., 2009), and therefore, magnetic cationic liposomes would enable the simultaneous delivery of SPIONs and pDNA into macrophages.…”

Development of magnetic anionic liposome/atelocollagen complexes for efficient magnetic drug targeting

“…For example, cationic liposomes have high monodispersity and stability because of their electrostatic repulsion (Bozzuto & Molinari, 2015 ). In addition, we and other groups have demonstrated that magnetic cationic liposomes (Mag-CL) electrostatically interact with the anionic regions of the cell surface, resulting in efficient cell uptake (Dandamudi & Campbell, 2007 ; Shido et al., 2010 ; Kono et al., 2017 ). However, cationic lipids and cationic polymers, which are major components of cationic liposomes, have been known to exhibit strong toxicity (Lv et al., 2006 ).…”