Solubilisation of dipalmitoylphosphatidylcholine bilayers by sodium taurocholate: A model to study the stability of liposomes in the gastrointestinal tract and their mechanism of interaction with a model bile salt

• Published in: European journal of pharmaceutics and biopharmaceutics 2009-02, Vol.71 (2), p.346-355
• Main Authors: Andrieux, Karine, Forte, Laura, Lesieur, Sylviane, Paternostre, Maité, Ollivon, Michel, Grabielle-Madelmont, Cécile
• Format: Article
• Language: English
• Subjects: 1,2-Dipalmitoylphosphatidylcholine - chemistry; 1,2-Dipalmitoylphosphatidylcholine - metabolism; Administration, Oral; Bile salt; Biological and medical sciences; Calorimetry, Differential Scanning; Crystallization; Drug Carriers - chemistry; Drug Carriers - metabolism; DSC; Gastrointestinal Tract - metabolism; General pharmacology; Liposome; Liposomes; Medical sciences; Models, Biological; Nephelometry and Turbidimetry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phosphatidylcholines - chemistry; Phospholipid; Polymorphism; Postprandial Period; Solubilisation mechanism; Solubility; Taurocholic Acid - metabolism; Temperature; Turbidity
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2008.09.004

In order to better understand the mechanism of destabilization of liposomes used as drug carriers for oral administration by bile salts, the insertion and partition of sodium taurocholate (TC) into small unilamellar vesicles (SUV) and multilayers (ML) of dipalmitoylphosphatidylcholine (DPPC) were examined by continuous turbidity analysis and DSC. Optical density was recorded during the progressive solubilisation of DPPC SUV and ML into DPPC/TC mixed micelles by varying the rate of TC addition and the temperature. The results show that the insertion and diffusion of TC in the DPPC membrane is a slow process influenced by the polymorphism of the lipid, independently of its organisation. This dynamic study mimics physiological phenomena of the digestion of liposomes. In the gastrointestinal tract, DPPC SUV would be more resistant to TC than egg phosphatidylcholine (EPC) SUV [K. Andrieux, L. Forte, S. Lesieur, M. Paternostre, M. Ollivon, C. Grabielle-Madelmont, Insertion and partition of sodium taurocholate into egg phosphatidylcholine vesicles, Pharm. Res. 21 (2004) 1505–1516] because of the lower insertion of TC into DPPC bilayer at 37 °C at low TC concentration in the medium (fasted conditions). At high TC concentration (postprandially or after lipid absorption), the use of DPPC to prepare liposomes will delay or reduce the liberation of a drug encapsulated into liposomes in the gastrointestinal tract. As a conclusion, the addition of DPPC appears an attractive strategy to formulate orally administered liposomes.