Transfer of lipid between triglyceride dispersions and lyotropic liquid crystal nanostructured particles using time-resolved SAXS

Abstract

Lipid-based lyotropic liquid crystalline nanostructured phases, such as the reverse bicontinuous cubic phase (V₂) and the reverse hexagonal phase (H₂), can be dispersed into submicron sized particles with often preserved internal nanostructure, termed cubosomes and hexosomes respectively. The internal nanostructure of the particles imparts desirable characteristics such as the ability to provide sustained release of active ingredients but is susceptible to change upon the incorporation of other lipids used as an active ingredient delivery system. These are complex systems in which the direction of lipid transfer, role of the stabiliser and formation of different phase structures, such as the frustrated H₂ phase are all likely to play a role but are not yet completely understood. Consequently, we have investigated the interparticle transfer of lipids between cubosomes/hexosomes and other dispersed lipids, namely triglycerides and vitamin E acetate emulsions. Time-resolved synchrotron small angle X-ray scattering was used to follow changes to nanostructure, attributed to the transfer of lipids into or out of the cubosomes. It was found that transfer of lipid occurred due to compositional ripening via a micelle-mediated mechanism, evident from the rate of lipid transfer increasing with Pluronic concentration. The rate of transfer of alkanes between liquid crystalline particles and emulsions has been shown previously to depend inversely on chain length. However in the triglyceride systems in the current study, the rate of lipid transfer (trilaurin > tricaprylin > supercooled trimyristin ≫ crystallised trimyristin and tristearin) did not decrease with increase in the chain length of triglyceride as might be anticipated. The equilibrium phase diagrams of triglyceride + phytantriol in excess water were determined. These diagrams showed that the transfer of phytantriol away from cubosomes to the emulsions, which increases the local triglyceride to phytantriol concentration in the cubosomes, would require formation of H₂ phase more readily for tricaprylin than for trilaurin. Therefore, the lack of correlation of transfer rate with chain length of the triglyceride was attributed to the system seeking to avoid the unfavourable formation of the H₂ phase, competing with the driving force from the entropy of mixing, and was therefore attributed as the reason for the greater rate of transfer of trilaurin compared to the less lipophilic tricaprylin.