The present study describes the effect of dissaccharides as lyoprotectant on phase modulation of lyophilized cationic dimethyl-dioctadecylammonium (DDA)-based liposomes. It has been shown that lyoprotectants such as dissaccharides i.e. sucrose, lactose and lactose preserve the lipid membranes during drying as the insertion of dissacharide molecules by restricting the space of the fatty acids and led to stabilize these membranes. The study revealed that the addition of dissaccharides in the formulation demonstrated a miscible mixture that might construct a stable dried liposomal formulation. DTA analysis showed that sucrose (5%w/v) applied to DDA liposomal formulation were miscible with the lipid mixtures; whereas lactose and mannitol at the same concentration 5% showed phase separation from the lipid mixtures in the dehydrated state and might trigger leakage that further affect the efficacy of the delivery systems. Furthermore, XRD and SEM analysis exhibited supporting evidents in which crystallinity of the formulation using sucrose was much less compared to lactose and mannitol. This might support the existence of physical interaction of dissaccharides with the lipid mixtures. Application of sucrose in low concentration (5%w/v)) revealed the lyoprotective mechanism that was based on ‘water replacement theory’; indicated by the depressed Tm of the freeze-dried lipid mixtures. Thus, in this particular study, we suggested that the protection of liposome formulations during the drying process was involving this mechanism. Addition of dissaccharides in the dried DDA formulation have prospective advantages as carrier system as they have been reported stabilizing the bilayer membrane.

Keywords: Liposomes, DDA, Sucrose, Lactose, Mannitol, Phase Modulation