(191v) Optimization of Double-Encapsulation System for Dermal Delivery of Macromolecules

Due to their high deformability and their compositions having structural similarity to skin lipids, liposomes have been extensively studied as facilitators of dermal delivery of macromolecules.  However, the major challenge for its application is that they are susceptible to factors such as changes in pH and temperature, or exposure to serum (Maurer et al. 1998 & Sulkowski et al. 2005).  To prevent the interaction of liposomes with an unfavorable physicochemical environment, a double-encapsulation formulation, in which liposomes were housed inside the internal aqueous droplets of double emulsion globules, was proposed and studied by using capillary video-microscopy (Wang et al. 2010).

In this study, oil-frozen, bulk double-encapsulation formulation was explored in in-vitro skin delivery of macromolecules, combining the benefits and synergism of the two delivery vehicles.  As with double emulsions storing and delivering non-encapsulated proteins (Rojas et al. 2007 & 2008), the solidification/freezing of the oil phase successfully preserved the emulsions’ stability for long periods of storage, and when the solid emulsions returned to room temperature and the oil phase thawed, the liposomes were released spontaneously.  Adsorption of lipids from the disassembled liposomes onto the W₁/O interface prevented the interaction between proteins and oil phase.  Thus, not only was the cutaneous delivery more efficient, but protein stability was also improved.

Three types of liposomes were used: L-α-phosphatidylcholine (PC) liposomes, Phospholipon 90H liposomes, and cationic liposomes consisted of N-[1-(2,3-Dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate (DOTAP) and PC.  The cationic liposomes showed higher encapsulation efficiency and lower leakage of macromolecules (ovalbumin), when compared to PC and Phospholipon 90H.  Additionally, high penetration ability of cationic liposomes and uptake by cells may be expected due to their positive surface charge.  Factors that influence the stability of double-encapsulation system and release of ovalbumin from double-encapsulation system were analyzed and optimized. 

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