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Multi-liposomal containers
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DOI：10.1016/j.cis.2015.08.011.png)
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Abstract
En 中文
Small unilamellar liposomes, 40-60 nm in diameter, composed of anionic diphosphatidylglycerol (cardiolipin, CL2-) or phosphatidylcerine (PS1-) and zwitter-ionic egg yolk lecithin (EL) or dipalmitoylphosphatidylcholine (DPPC), electrostatically complex with polystyrene microspheres, ca. 100 nm in diameter, grafted by polycationic chains (spherical polycationic brushes, SPBs). Polymer/liposome binding studies were carried out using electrophoretic mobility (EPM), dynamic light scattering (DLS), fluorescence, conductometty, differential scanning calorimetry (DSC), and cryogenic transmission electron microscopy (cryo-TEM) as the main analytical tools. By these means a remarkably detailed picture emerges of molecular events inside a membrane. The following are among the most important conclusions that arose from the experiments: (a) binding of liposomes to SPBs is accompanied by flip-flop of anionic lipids from the inner to the outer leaflet of the liposomal membrane along with lateral lipid segregation into islands. (b) The SPB-induced structural reorganization of the liposomal membrane, together with the geometry of anionic lipid molecules, determines the maximum molar fraction of anionic lipid (a key parameter designated as v) that ensures the structural integrity of liposomes upon complexation: v = 0.3 for liposomes with conically-shaped CL2- and v = 0.5 for liposomes with anionic cylindrically-shaped PS1-. (c) The number of intact liposomes per SPB particle varies from 40 for (v = 0.1) to 13 (v = 0.5). (d) By using a mixture of liposomes with variety of encapsulated substances, multi-liposomal complexes can be prepared with a high loading capacity and a controlled ratio of the contents. (e) In order to make the mixed anionic liposomes pH-sensitive, they are additionally modified by 30 mol% of a morpholinocyclohexanol-based lipid that undergoes a conformational flip when changing pH. Being complexed with SPBs, such liposomes rapidly release their contents when the pH is reduced from 7.0 to 5.0. The results allow loaded liposomes to be concentrated within a rather small volume and, thereby, the preparation of multi-liposomal containers of promise in the drug delivery field. (C) 2015 Elsevier B.V. All rights reserved.
Keywords:
Anionic liposome
Spherical polycationic brush
Multi-liposomal complex
Flip-flop
Lateral lipid segregation
pH-sensitivity
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