Structural Versatility of Bicellar Systems and Their Possibilities as Colloidal Carriers

Abstract

Bicellar systems are lipid nanostructures formed by long- and short-chained phospholipids dispersed in aqueous solution. The morphological transitions of bicellar aggregates due to temperature, composition and time variations have been revised in this work. To this end, two bicellar systems have been considered; one formed by dimyristoyl-phosphatidylcholine (DMPC) and dihexanoyl- phosphatidylcholine (DHPC) and another formed by dipalmitoyl-phosphatidylcholine (DPPC) and DHPC. The relationship between the magnetic alignment, the morphology of the aggregates and the phase transition temperature (Tm) of lipids is discussed. In general terms, the non-alignable samples present rounded objects at temperature below the Tm. Above this temperature, an increase of viscosity is followed by the formation of large elongated aggregates. Alignable samples presented discoidal objects below the Tm. The best alignment was achieved above this temperature with large areas of lamellar stacked bilayers and some multilamellar vesicles. The effect of the inclusion of ceramides with different chain lengths in the structure of bicelles is also revised in the present article. A number of physical techniques show that the bicellar structures are affected by both the concentration and the type of ceramide. Systems are able to incorporate 10% mol of ceramides that probably are organized forming domains. The addition of 20% mol of ceramides promotes destabilization of bicelles, promoting the formation of mixed systems that include large structures. Bicellar systems have demonstrated to be morphologically stable with time, able to encapsulate different actives and to induce specific effects on the skin. These facts make bicellar systems good candidates as colloidal carriers for dermal delivery. However, water dilution induces structural changes and formation of vesicular structures in the systems; stabilization strategies have been been explored in recent works and are also updated here.

Lipid Concentration and Molar Ratio Boundaries for the Use of Isotropic Bicelles

“… 1 , 2 These membranes mimetics are most commonly composed of dimyristoylphosphatidylcholine (DMPC) which organize in a bilayer stabilized by short-chain dihexanoylphosphatidylcholines (DHPC) in high curvature regions 3 − 8 of discs or perforated vesicles. 3 − 5 , 9 − 12 Although the morphology of bicelles is debated, the planar region made of long-chain phospholipids constitutes a favorable environment to study molecular interactions as well as the structure of membrane peptides and proteins with different biophysical techniques such as nuclear magnetic resonance (NMR), X-ray crystallography, circular dichroism (CD), and Fourier transform infrared (FTIR) spectroscopy. 3 − 5 , 10 , 13 − 18 Most interestingly, for solid-state NMR applications, bicelles are known to spontaneously orient in a magnetic field in excess of 1 T at high DMPC/DHPC molar ( q ) ratios (above 2.3) and within well-defined total lipid concentrations (3–60% w/v) and temperatures (30–50 °C).…”

Lipid Membrane Mimetics in Functional and Structural Studies of Integral Membrane Proteins

“…They can also be formed by mixing the long-chain lipids 1,2-dimyristoil-sn-Glycero-3-[Phospho-rac-(1-glycerol)] (DMPG) and DMPC with the short-chain lipid DHPC [ 141 , 142 ]. Bicellar nanostructures comprising various lipids with incorporated cholesterol, ceramides, cardiolipin, and more have also been developed [ 143 , 144 , 145 ].…”

“…However, it is difficult to precisely estimate bicelle size. For example, bicelles made of DMPC/DHPC had an estimated average size of 20 nm at q = 2 [ 143 ], and those made of DMPC/DMPG/DHPC at q = 2.6 had an estimated average size of 10 nm [ 149 ]. This discrepancy can be explained by the limitations of different methods used to determine bicelles’ size.…”

“…Another disadvantage of conventional bicelles is that their size and geometry depend on the total lipid concentration in the solution; therefore, any dilution changes the system properties. At high dilutions, bicelle-to-vesicle transitions can occur [ 143 ], so care must be taken to maintain constant lipid concertation throughout the experiment. Attempts were made to overcome this deficiency via kinetically stable bicelles, such as those comprising a mixture of the phospholipid 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and a sodium cholate-derived surfactant (SC-C5) at room temperature.…”

Conformational dynamics of α-synuclein during the interaction with phospholipid nanodiscs by Millisecond Hydrogen Deuterium Exchange Mass Spectrometry

“…Formation of nanodiscs was monitored by 31 P NMR ( Figure S2) and ESI-MS. In the case of NMR, intact nanodiscs were identified via a characteristic sharp peak at 0ppm (80)(81)(82). By ESI-MS, nanodiscs generate a broad 'hump-like' peak resulting from incomplete desolvation and polydispersity in the number of lipids contained in individual nanodiscs ( Figure 2c) (83)(84)(85).…”