Stability of liposomes containing bio-enhancers and tetraether lipids in simulated gastro-intestinal fluids

• Published in: International journal of pharmaceutics Vol. 405; no. 1; pp. 210 - 217
• Main Authors: Parmentier, Johannes, Becker, Matthias M.M., Heintz, Udo, Fricker, Gert
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 28-02-2011; Elsevier
• Subjects: Bile salts; Biological and medical sciences; Cholesterol - chemistry; Dextrans - administration & dosage; Dextrans - pharmacokinetics; Drug Delivery Systems; Drug Stability; Dynamic light scattering; Enhancers; Fluorescein-5-isothiocyanate - administration & dosage; Fluorescein-5-isothiocyanate - analogs & derivatives; Fluorescein-5-isothiocyanate - pharmacokinetics; Fluoresceins - administration & dosage; Fluoresceins - chemistry; Fluoresceins - pharmacokinetics; Fluorescent Dyes - chemistry; Gastrointestinal Tract; General pharmacology; Glyceryl Ethers - chemistry; Hydrogen-Ion Concentration; Lipids; Liposomes; Liposomes - chemistry; Medical sciences; Oral delivery; Pancreatin - chemistry; Permeability; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phosphatidylcholines - chemistry; Taurocholic Acid - chemistry; Tetraether lipids; Tetraether lipids; Enhancers; Liposomes; Dynamic light scattering; Oral delivery; Stability; Pharmaceutical technology; Light scattering; Gut; Oral administration; Liposome; Lipids; Physicochemical properties
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2010.12.005

Stable EPC/cholesterol based liposomes with bio-enhancers and tetraether lipids can be formed. They show a low release of FITC-dextran in pH 2 buffer, sodium taurocholate and pancreatin.
The stability of egg phosphatidylcholine (EPC) and cholesterol (Chol) based liposomes and liposomes with the addition of the tetraether lipid glycerylcaldityl tetraether (GCTE) and the bio-enhancers cholylsarcosine, octadecanethiol and TPGS 1000 in Tris buffer pH 2, sodium taurocholate 10
mM and pancreatin was compared. At pH 2 all formulations released nearly 100% of the small hydrophilic fluorescent marker carboxyfluorescein (CF) within the first 10
min, whereas they were mostly stable in size as confirmed by dynamic light scattering (DLS) measurements. Also leakage of the macromolecule FITC-dextran 70
kDa over 60
min at pH 2 was at most 23.9%. After 20
min in 10
mM sodium taurocholate vesicles without GCTE showed a release of CF between 84.0% and 89.5%. In contrast, GCTE-stabilised formulations after 90
min in sodium taurocholate exhibited a CF release between 36.6% and 69.0% depending on the addition of bio-enhancers. Pancreatin had a minor influence on liposome stability in all assays. It is possible to form EPC/Chol vesicles containing different types of bio-enhancers and to stabilise them with GCTE against bile salts. This type of liposomes could be a versatile tool for the oral delivery of drug substances with poor stability in the GI tract and low permeability.