Enhanced oral absorption of insulin-loaded liposomes containing bile salts: a mechanistic study.
Liposomes containing bile salts (BS-liposomes) significantly enhanced the oral bioavailability of insulin (rhINS). However, the underlying absorption mechanisms have not been well understood yet. In this study, the transiting fate of the liposomes was first investigated using fluorescent imaging tools to confirm the effect of enhanced gastrointestinal stability. In order to obtain evidence of enhanced transcellular permeation, the interaction between BS-liposomes and the biomembrane was investigated in Caco-2 cell lines. BS-liposomes were found to be more stable in the gastrointestinal tract by showing prolonged residence time in comparison with conventional liposomes. BS-liposomes were significantly more effective for cellular uptake and transport of rhINS; and this effect was found to be size- and concentration-dependent. A good linear correlation was observed between the concentration of the liposomes and uptake/transport of rhINS. Confocal laser scanning microscopy visualization further validated the transcellular transit of BS-liposomes. The BS-liposomes showed little effect on cytotoxicity and did not induce apoptosis within 24h investigation. It was concluded that BS-liposomes showed improved in vivo residence time and enhanced permeation across the biomemebranes. Mechanisms of trans-enterocytic internalization could be proposed as an interpretation for enhanced absorption of insulin-loaded liposomes.
['Niu|Mengmeng|M|', "Tan|Ya'nan|Y|", 'Guan|Peipei|P|', 'Hovgaard|Lars|L|', 'Lu|Yi|Y|', 'Qi|Jianping|J|', 'Lian|Ruyue|R|', 'Li|Xiaoyang|X|', 'Wu|Wei|W|']
D000284:Administration, Oral D000818:Animals D017209:Apoptosis D001647:Bile Acids and Salts D018938:Caco-2 Cells D002470:Cell Survival D041981:Gastrointestinal Tract D006801:Humans D007328:Insulin D007408:Intestinal Absorption D008081:Liposomes D008297:Male D051381:Rats D017208:Rats, Wistar D011994:Recombinant Proteins
Liposomes Bile salt Insulin Cellular uptake Transport Cytotoxicity