Highly Hydrophilic Fused Aggregates (Microsponges) from a C12 Spermine Bolaamphiphile

Abstract

Bolaamphiphiles consist of two hydrophilic headgroups joined by a hydrophobic linker. They are known to self-assemble into vesicles, micelles, tubules and fibers. Here we report on the self-assembly of a 1,12-[N,N-bis(3-aminopropyl)-1,4-butane diamine] dodecane (12G1) in aqueous media into discrete nonbilayer nanoparticles and unusual fused highly hydrated sponge like structures. 12G1, 1,10-[ N,N-bis(3-aminopropyl)-1,4-butane diamine] decane (10G1), 1,8-[N,N-bis(3-aminopropyl)-1,4-butane diamine] octane (8G1), and 1-[N,N-bis(3-aminopropyl)-1,4-butane diamine] dodecane (12G0) were synthesized and their self-assembly studied. 12G0 was relatively insoluble in water and multilamellar vesicles were produced with this amphiphile and cholesterol. While no aggregation in aqueous media was recorded for either 10G1 or 8G1 up to a concentration of 20 mM, aggregation of 12G1 molecules was seen to take place at an aqueous concentration of 1.75 mM as determined using various fluorescent and colorimetric probes and surface tension measurements. Electron microscopy images revealed that 12G1 formed monolayer vesicles of 20 nm in size at a concentration of 2.6 mM and even larger fused aggregates when the concentration was increased to 35 mM. Fusion resulted from the bridging of vesicles by the bolaamphiphile molecules. 12G1 aggregates encapsulated 23X more low molecular weight (4kD) FITC-dextran than high (250kD) molecular weight FITC-dextran, an indication of the limited volume of the hydrophilic domains. 12G1 also encapsulated 137X more 4kD FITC-dextran than was encapsulated by conventional sorbitan monostearate vesicles. We conclude that highly hydrated aggregates consisting of fused monolayer vesicles with small discrete hydrophilic domains in a sponge like structure may be formed by the self-assembly of bolaamphiphiles.