The aggregation behavior of dipalmitoylphosphatidylcholine (DPPC) mixed with dodecyl β-d-glucopyranoside (DG) and/or dodecyl β-d-maltoside (DM) was studied in excess buffer. From high-performance liquid chromatography on a gel exclusion column and quasi-elastic light scattering, ultrasonic irradiation of DPPC−DG mixtures yields closed unilamellar vesicles for DG-to-DPPC molar ratios smaller than 1.8, above which some discoid structures are seen by cryofracture electron microscopy. Solubilization by DM of pure DPPC and DPPC−DG vesicles was followed at 37 °C. Turbidity recordings reveal seven significant break points corresponding to the limits separating distinct aggregation states and corresponding to a precise partitioning of DM between lipid aggregates and buffer. Three of these limits coincide with the boundaries of four distinct phase domains revealed by SAXS performed on more concentrated samples over the same composition range. At 37 °C, with increasing DM-to-DPPC ratios, (1) fully hydrated lamellar structures, (2) coexisting lamellar and micellar assemblies, (3) mixed micelles separating from the aqueous phase, and (4) isotropic micellar solutions successively appear. The sequence of these phases is sensitive to temperature variations; bilayer formation is favored by heating. Domain 3 is attributed to a cloud point phenomenon occurring in the micellar region at temperatures higher than 30 or 34 °C, with or without DG, respectively.

Partial pseudo-binary-phase diagrams of dipalmitoylphosphatidylcholine (DPPC) and two glycosidic surfactants, dodecyl-β-d-maltoside (DM) and dodecyl-β-d-glucopyranoside (DG) in excess aqueous buffer were investigated by differential scanning calorimetry and X-ray diffraction, in the 10−50 °C (DPPC−DG) and 20−50 °C (DPPC−DM) temperature intervals and in the 0−1.8 range of surfactant molar ratios. At low levels, both DG and DM behaved as lipid-soluble impurities, preserving the lamellar organizations of the pure phospholipid in excess water. With an increase in the surfactant contents, the phase behaviors of DPPC in mixture with DG or DM diverged:  while the DPPC−DG system exhibited only mixed lamellar structures, the DPPC−DM system underwent bilayer-to-micelle transitions beyond nearly 1 DM molecule per 2 phospholipids. For both systems, the melting of the DPPC hydrocarbon chains induced two isothermal (solid → solid + liquid) reactions, indicating a nonideal mixing in the surfactant-rich solid phases. At low temperatures, DPPC−DG and DPPC−DM mixtures formed likewise lamellar organizations with straight hydrocarbon chains. However, at DM molar ratios >0.4, the lamellar structures were broken up into micelle-like aggregates with a solid core. At high temperatures, both pseudobinary diagrams showed the existence of fluid lamellar phases, the periodicity of which was governed by the DG or DM insertion but depending on the surfactant headgroup. DG principally decreased the bilayer thickness due to the reduction of the mean chain length of the DPPC−DG mixtures. At molar ratios <0.4, DM followed the DG behavior, while at higher contents a significant lamellar swelling was observed that coincided with the appearance of mixed micelles.

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An enzymatic procedure for liposome formation through micelle to vesicle transition is described. Amyloglucosidase hydrolysis of dodecyl--D-maltoside (DM) giving dodecyl--D-glucoside (DG) leads to dipalmitoylphosphatidylcholine (DPPC)-based vesicle formation from DPPC-DM mixed micelles. Starting from a 1.8 DM/DPPC molar ratio corresponding to mixed micelles, progressive hydrolysis of DM gives DPPC-DG-DM intermediate aggregates ending with DPPC-DG vesicles upon reaction completion. Initial steps of the process corresponding to the exit of the micellar domain were followed by turbidimetry measurements. Next, the reaction progress was investigated by RP-HPLC, HPLC-GEC, and cryofracture electron microscopy. A constant reaction rate is observed in the micellar domain, while the increase of the lamellae proportion considerably decreases the enzyme catalytic activity. Finally, the enzymatic hydrolysis is significally slowed when closed vesicles are formed. Enzymatic activity is dependent on DM availability in the bulk phase and of the DM/DPPC molar ratio in the aggregates. The presence of mixed micelles or lamellar sheets considerably modulates DM monomer concentration in the aqueous phase. The liposomes formed by the enzymatic process are spherical, unilamellar, and heterogeneous in size with a mean diameter ranging from 10 to 80 nm.