Kinetically Stable Bicelles with Dilution Tolerance, Size Tunability, and Thermoresponsiveness for Drug Delivery Applications

Abstract

Mixtures of a phospholipid (1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine, DPPC) and a sodium-cholate-derived surfactant (SC-C ) at room temperature formed phospholipid bilayer fragments that were edge-stabilized by SC-C : so-called "bicelles". Because the bilayer melting point of DPPC (41 °C) is above room temperature and because SC-C has an exceptionally low critical micelle concentration (<0.5 mm), the bicelles are kinetically frozen at room temperature. Consequently, they exist even when the mixture is diluted to a concentration of 0.04 wt %. In addition, the lateral size of the bicelles can be fine-tuned by altering the molar ratio of DPPC to SC-C . On heating to ≈37 °C, the bicelles transformed into micelles composed of DPPC and SC-C . By taking advantage of the dilution tolerance, size tunability, and thermoresponsiveness, we demonstrated in vitro drug delivery based on use of the bicelles as carriers, which suggests their potential utility in transdermal drug delivery.

Lipid-Based Intelligent Vehicle Capabilitized with Physical and Physiological Activation

“…The SPION increased temperature 37 °C to 43 °C by stimulation of alternating magnetic field (AMF), and sustained release of temozolomide resulting into apoptosis and in the subsequent death of glioblastoma cells. (c) edge stabilizer SC-C5 gives bicelles dilution tolerance and thermoresponsiveness since it has extremely low CMC [38]; (d) thermosensitive on/off switch liposome achieves a reversible drug release on demand [40].…”

Amphiphilic Micelles as Superior Nanocarriers in Drug Delivery: from Current Preclinical Surveys to Structural Frameworks

“…These long‐chain phospholipids are bounded by a border of short chain phospholipid that shields its tail from water. The ratio of short‐chain to long‐chain phospholipid (q) along with the total concentration of phospholipid (CL) regulates the size of bicelle formed [107] . The dimyristoylphosphatidylcholine(DMPC) that is taken as long‐chain phospholipid constituent and is doped with phospholipids having same alkyl chain length but diverse head group e. g. dimyristoylphosphatidylglycerol (DMPG) and dimyristoyl phosphatidyl‐serine (DMPS) are taken to alter the interfacial charge characteristics and produce malleability of phospholipid composition [108] .…”

“…The ratio of short-chain to long-chain phospholipid (q) along with the total concentration of phospholipid (CL) regulates the size of bicelle formed. [107] The dimyristoylphosphatidylcholine(DMPC) that is taken as longchain phospholipid constituent and is doped with phospholipids having same alkyl chain length but diverse head group e. g. dimyristoylphosphatidylglycerol (DMPG) and dimyristoyl phosphatidyl-serine (DMPS) are taken to alter the interfacial charge characteristics and produce malleability of phospholipid composition. [108] The bilayered micelle stability is explained in terms of the short-chain lipids in the regions of the high bend, which in turn lowers the edge energy of self-associates.…”

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

“…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. These bicelles' stability results from the high melting temperature of DPPC (41 °C) and a very low SC-C5 CMC (<0.5 mM) [158]. Generally, geometric arguments can help to estimate the bicelle's size using the molar ratio between long-and short-chain lipids (or detergent); this so-called q value (Equation ( 1)) to calculate the radius of the bicelle's bilayer region (R) directly, in addition to the bicelle's topology and size [146][147][148].…”

“…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. These bicelles’ stability results from the high melting temperature of DPPC (41 °C) and a very low SC-C5 CMC (<0.5 mM) [ 158 ].…”