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

Xiuying Li¹, Dan Chen¹, Chaoyi Le², Chunliu Zhu¹, Yong Gan¹, Lars Hovgaard³, Mingshi Yang^4
1Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; ²University of Toronto Mississauga Campus, Ontario, Canada; ³Oral Formulation Development, Novo Nordisk A/S, Maalov; ⁴Department of Pharmaceutics and Analytical Chemistry, University of Copenhagen, Copenhagen, Denmark

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.

Keywords: Pluronic F127, mucus-penetrating, particles, liposomes, oral drug delivery