ABSTRACT
A series of 1,3-diamido phosphocholines was synthesized, and their potential to form stable bilayers was investigated. Large and giant unilamellar vesicles produced from these new lipids form a wide variety of faceted liposomes. Factors such as cooling rates and the careful choice of the liposome preparation method influence the formation of facets. Interdigitation was hypothesized as a main factor for the stabilization of facets and effectively monitored by small-angle X-ray scattering measurements.
Subject(s)
Lipid Bilayers/chemistry , Phospholipids/chemistry , Scattering, Small Angle , Temperature , Unilamellar Liposomes/chemistry , X-Ray DiffractionABSTRACT
Atherosclerosis results in the narrowing of arterial blood vessels and this causes significant changes in the endogenous shear stress between healthy and constricted arteries. Nanocontainers that can release drugs locally with such rheological changes can be very useful. Here, we show that vesicles made from an artificial 1,3-diaminophospholipid are stable under static conditions but release their contents at elevated shear stress. These vesicles have a lenticular morphology, which potentially leads to instabilities along their equator. Using a model cardiovascular system based on polymer tubes and an external pump to represent shear stress in healthy and constricted vessels of the heart, we show that drugs preferentially release from the vesicles in constricted vessels that have high shear stress.
Subject(s)
Cardiovascular System/drug effects , Drug Delivery Systems , Ethanolamines , Nanostructures/chemistry , Phospholipids/chemistry , Arteries/drug effects , Arteries/pathology , Ethanolamines/chemical synthesis , Ethanolamines/chemistry , Ethanolamines/pharmacology , Humans , Lipids/chemistry , Rheology , Stress, MechanicalABSTRACT
Two complementary artificial diether phospholipids were synthesized that can undergo a Cu(I)-catalyzed Huisgen-Sharpless click reaction. The resulting lipid can bridge the membranes of large unilamellar vesicles and cause their aggregation and ultimately their fusion.
Subject(s)
Phospholipids/chemistry , Triazoles/chemistry , Catalysis , Click Chemistry , Copper/chemistry , Molecular Structure , Particle Size , Phospholipids/chemical synthesis , Surface PropertiesABSTRACT
Both enantiomers of TRISPHAT anion can be obtained on a multigram scale through a novel resolution procedure. The Lambda enantiomer is isolated as the tri-n-butylammonium salt, [(n)()Bu(3)NH][Lambda-1], which is soluble in pure CHCl(3) and CH(2)Cl(2). The Delta enantiomer is prepared as the cinchonidinium derivative, which is only soluble in polar solvent mixtures (>7.5% DMSO in CHCl(3)).
