Fine-tuning of POPC liposomal leakage by the use of β-cyclodextrin and several hydrophobic guests

Abstract

The effect of entrapped β-cyclodextrin (β-CD) on the stability of multilamellar vesicles (MLVs) of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), prepared by the dehydration-rehydration method, was studied by monitoring the release of 5(6)-carboxyfluorescein encapsulated into the liposomes. Different hydrophobic guests, such as Fullerene C₆₀, have been incorporated into the POPC bilayer in order to modify the membrane composition. The kinetic results as well as ESI-MS measurements evidenced that the destabilizing activity of β-CD is due to the formation of β-CD inclusion complexes and the consequent removal of selected bilayer constituents from the liposomal membrane. Hence, when β-CD was added to the liposomes in the form of a strong, water-soluble 2:1 β-CD/C₆₀ inclusion complex, such a destabilizing effect was not observed. However, the same β-CD/C₆₀ inclusion complex does not form as a result of C₆₀ extraction from the bilayer. This may be attributed either to the overwhelming concentration of POPC with respect to C₆₀ and/or to the fact that C₆₀ is largely aggregated in the bilayer. Turbidimetric and fluorimetric determinations of lamellarity and entrapped volume of the studied MLVs provided further evidence of the alteration of the liposomal bilayer as a consequence of the addition of β-CD and/or the presence of the studied guests.

Keywords::

• Liposomal leakage
• β-cyclodextrin
• lamellarity
• Fullerene C₆₀
• ESI-MS
• 1,2-dipalmitoyl-sn-glycero-3-phospho-ethanolamine-N-[methoxy-(polyethylene glycol)-2000] ammonium salt