Cationic liposomes in double emulsions for controlled release

[Display omitted] ► Double-encapsulation formulations were fabricated by incorporating liposomes as the W1 phase of W1/O/W2 double emulsions. ► Cryo-SEM images showed that liposomes are well encapsulated within the W1 phase. ► The release mechanism upon the freeze–thaw treatment is internal coalescence followed by external coalescence. ► The release of liposomes and FITC-BSA upon the freeze–thaw treatment is gradual rather than instant from the W1 phase. ► The release rate can be controlled by tuning the concentration of PC lipids in the liposomes. Liposomes containing a model active component were entrapped within the internal aqueous phase (W1) of W1/O/W2 double emulsions, thus providing a double-encapsulation system. Our motivation for the development of this system is to prevent liposomes from interacting with unfavorable physicochemical conditions and to optimize this system for dermal vaccine delivery. The choice of cationic liposomes is based on the fact that they have high penetration ability across the skin and hair follicles, and an adjuvant effect on the activation of antigen-presenting cells. Cryo-SEM images showed that liposomes are well encapsulated within the W1 phase, indicating that most liposomes remain intact during the homogenization step of formulation fabrication. Freezing the n-hexadecane oil (O) phase of the double-encapsulation formulations preserved their stability during the storage, and subsequent oil-thawing induced progressive release of liposomes and their contents. The release mechanism upon the freeze–thaw treatment was internal coalescence followed by external coalescence. Our results also indicated that tuning the concentration of l-α-phosphatidylcholine (PC) lipid in the cationic liposomes can control the release rate from the double-encapsulation formulations.