Vesosome, a multi-compartment structure consisting of drug-loaded liposomes encapsulated within another bilayer, is a promising drug carrier with better retention and stability compared with unilamellar liposomes. The vesosome preparation takes advantage of the interdigitated phase of saturated lipids, which causes lipid bilayers to form flat, open sheets at low temperature, that close to form large unilamellar vesicles at higher temperatures. Adding poloxamer 188 (P188) to the Dipalmitoylphosphocholine (DPPC) interdigitated sheets prior to closure leads to ~ 0.6 µm diameter vesosomes. Applying osmotic pressure by diluting the vesosomes with buffer of increased salt concentration can further decrease the vesosome diameter by 10%. Freeze-fracture TEM and light scattering were used to evaluate the size distribution and polydispersity of the vesosomes formed. Nearly monodisperse hollow gold nanospheres with absorbance wavelength in the visible and infrared range have been synthesized and loaded inside vesosome to be externally triggered via near Infra-Red light for controlled drug release.