Encapsulation of Zwitterionic Au Nanocrystals into Liposomes by Reverse Phase Evaporation Method: Influence of the...

Since both liposomes and nanoparticles have shown great potential in application for clinical diagnostics and therapeutics, the perfect combination of the two materials is appealing for further improving the theranostic effect. Therefore, fabrication of liposomes loaded with nanoparticles in a controllable manner is desirable. Detection of various factors affecting encapsulation needs to be assigned. Here, we use zwitterionic Au nanoparticles (Au_±NPs) coated with a mixture of 11-mercaptoundecanoic acid and N,N,N-trimethyl(11-mercaptoundecyl) ammonium chloride to study their encapsulation behavior by reversed phase evaporation (REV) method. To produce a reverse emulsion, an organic solution of dipalmitoylphosphatidylcholine (DPPC) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (ammonium salt) (PEG2000-DOPE) is mixed with an aqueous Au_±NP colloidal solution under sonication. The pH of the colloidal solution controls the surface charge of the Au_±NPs and then tunes the interactions between Au_±NPs and phospholipids. At lower pH, the positive surface charges favor Au_±NP transfer into the organic phase and consequently prevent their encapsulation into liposomes. The efficiency in encapsulation is markedly improved by increasing the pH of the Au_±NP colloidal solution. The highest efficiency is obtained at a pH value slightly larger than the isoelectric point. Further pH increase induces a decrease in encapsulation efficiency. This is due to increase of the repulsive forces between Au_±NPs and phospholipids indicating that both the nature (positive or negative) and the amount of surface charge are key parameters in the encapsulation efficiency. We also find that the increase in Au_±NP concentration favors the encapsulation process.