Novel mucus-penetrating liposomes as a potential oral drug delivery system: preparation, in vitro characterization, and enhanced cellular uptake

Abstract

Background The aim of this study was to investigate the intestinal mucus-penetrating properties and intestinal cellular uptake of two types of liposomes modified by Pluronic F127 (PF127). Methods The two types of liposomes, ie, PF127-inlaid liposomes and PF127-adsorbed liposomes, were prepared by a thin-film hydration method followed by extrusion, in which coumarin 6 was loaded as a fluorescence marker. A modified Franz diffusion cell mounted with the intestinal mucus of rats was used to study the diffusion characteristics of the two types of PF127 liposomes. Cell uptake studies were conducted in Caco-2 cells and analyzed using confocal laser scanning microcopy as well as flow cytometry. Results The diffusion efficiency of the two types of PF127-modified liposomes through intestinal rat mucus was 5–7-fold higher than that of unmodified liposomes. Compared with unmodified liposomes, PF127-inlaid liposomes showed significantly higher cellular uptake of courmarin 6. PF127-adsorbed liposomes showed a lower cellular uptake. Moreover, and interestingly, the two types of PF127-modified liposomes showed different cellular uptake mechanisms in Caco-2 cells. Conclusion PF127-inlaid liposomes with improved intestinal mucus-penetrating ability and enhanced cellular uptake might be a potential carrier candidate for oral drug delivery.

PEG modified liposomes containing CRX-601 adjuvant in combination with methylglycol chitosan enhance the murine sublingual immune response to influenza vaccination

“…Such surface neutral nanoparticles [9-11, 28] and Pluronic F127 modified liposomes [13, 14] have previously been reported to be muco-inert/mucus penetrating, allowing rapid diffusion through the mucus to the underlying epithelium. Our evaluation of various PEG polymers indicates that phospholipid-PEG conjugates (PE-PEG2K/PE-PEG5K) were more efficient in achieving surface charge neutralization on CRX-601 loaded liposomes compared to Pluronic copolymers (Table 2).…”

“…Such particles, termed mucoinert or mucus penetrating by the authors, were achieved by chemical coupling of low–molecular weight poly(ethylene glycol) (PEG) at high densities on solid nanoparticles [10, 11] or self-assembly of amphiphilic PEG copolymers [12]. Others have described Pluronic F127 coated mucus penetrating liposomes for delivery across the intestinal mucus [13, 14]. However, the effectiveness of mucus penetration, at least for PLGA and polystyrene based systems, has been reported to be highly dependent on the PEG chain length and density [11].…”

Liposome-based mucus-penetrating particles (MPP) for mucosal theranostics: Demonstration of diamagnetic chemical exchange saturation transfer (diaCEST) magnetic resonance imaging (MRI)

“…8 Although liposomal systems have been explored for mucosal delivery, 9, 10 there has not been a focus on directly observing the interactions of liposomal formulations with mucus, and how these interactions impact mucosal distribution. Here, we varied the composition of PEG-conjugated lipids to investigate the effect of PEG surface density on liposome mobility in human cervicovaginal mucus (CVM) and vaginal distribution in vivo .…”

Biophysical characterization of small molecule antiviral-loaded nanolipogels for HIV-1 chemoprophylaxis and topical mucosal application

“…This indicates that the delivered ARV drugs were still present at protective concentrations, 24-hours post-vaginal administration in mice. Previous studies have shown that EPC liposomes have low diffusivity in rat intestinal mucus [43]. We hypothesize that the observed antiviral activity is likely due to entrapment of a small fraction of the administered dose in freshly produced mucus in the mouse genital tract.…”