Size and Phase Control of Cubic Lyotropic Liquid Crystal Nanoparticles

The effective use of lyotropic liquid crystalline dispersions, such as cubosomes, as drug delivery vehicles requires that they have tailored physical characteristics that suit specific therapeutics and external conditions. Here, we have developed phytantriol-based cubosomes from a dispersion of unilamellar vesicles and show that we can control their size as well as the critical packing parameter (CPP) of the amphiphilic bilayer through regulation of temperature and salt concentration, respectively. Using the anionic biological lipid 1,2-dipalmi-toylphosphatidylserine (DPPS) to prevent the cubic phase from forming, we show that the addition of phosphate buffered saline (PBS) results in a transition from small unilamellar vesicles to the cubic phase due to charge-shielding of the anionic lipid. Using dynamic light scattering, we show that the cubosomes formed following the addition of PBS are as small as 30 nm; however, we can increase the average size of the cubsosomes to create an almost monodisperse dispersion of cubosomes through cooling. We propose that this phenomenon is brought about through the phase separation of the Pluronic F-127 used to stabilize the cubosomes. To complement previous work using the salt-induced method of cubosome production, we show, using synchrotron small-angle X-ray scattering (SAXS), that we can control the CPP of the amphiphile bilayer which grants us phase and lattice parameter control of the cubosomes.