Comparative study of Pluronic(®) F127-modified liposomes and chitosan-modified liposomes for mucus penetration and oral absorption of cyclosporine A in rats.

Liposomes modified using cationic and hydrophilic nonionic polymers are 2 popular carriers for improving oral drug absorption. Cationic polymer-modified liposomes can adhere to the intestinal wall mucus (mucoadhesive type), while liposomes modified using hydrophilic nonionic polymers can penetrate across the mucus barrier (mucus-penetrating type). Chitosan-modified liposomes (CS-Lip, mucoadhesive type) and Pluronic(®) F127-modified liposomes (PF127-Lip, mucus-penetrating type) were engineered to investigate the differences between these mucoadhesive and mucus-penetrating systems in oral absorption of a poorly soluble drug, cyclosporine A (CyA). Stability of CS-Lip and PF127-Lip was studied in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The intestinal mucus adhesion or penetration of liposomes was studied by confocal laser scanning microcopy and fluorophotometry using coumarin 6 as the fluorescent probe. The oral absorption of CyA-loaded liposomes was also studied in Sprague-Dawley rats. In vitro and in vivo studies revealed that CS-Lip tended to aggregate in SIF, to be trapped by mucus, to remain mainly in the upper portion of the intestinal tract, and to show limited penetration ability. In contrast, PF127-Lip were more stable in the SIF and SGF, were found throughout the intestinal tract, and were able to penetrate the mucus layers to reach the epithelial surface. Pharmacokinetic analysis in rats showed that the Cmax and AUC0-t of PF127-Lip were 1.73- and 1.84-fold higher than those of CS-Lip, respectively (P<0.05). In conclusion, the stability and mucus-penetrating ability of PF127-Lip in the gastrointestinal tract rendered it more suitable than the mucoadhesive CS-Lip for oral delivery CyA.