Effects of Aluminum Adjuvant Compounds, Tweens, and Spans on the Stability ofLiposome Permeability

摘要

The ability of liposomes to retain their integrity and to serve as permeabilitybarriers for encapsulated antigen, properties that are theoretically important for optimal adjuvant activity, was breached when the liposomes were absorbed to aluminum hydroxide gels. Stability of liposomal permeability was assessed by using either glucose or prostate specific antigen (PSA) as an encapsulated aqueous marker. Liposomes composed of dimyristoyl phosphatidylcholine, dimyristoyl phosphatidylglycerol, cholesterol, and lipid A were destabilized following absorption to aluminum adjuvant compounds, resulting in release of trapped glucose or encapsulated PSA, respectively. The release, which increased linearly with time in a temperature-dependent manner, was more than three-fold higher in the case of encapsulated PSA than with trapped glucose. It was independent of the phospholipid structure and the liposomal surface charge. The destabilization of aluminum-absorbed liposomes was reversed in a concentration-dependent manner by incorporation of fatty acid esters of polyoxyethylene sorbitan (Tweens), but not by fatty acid esters of sorbitan (Spans), into the liposomal lipid bilayer. We conclude that Tweens can serve as useful constituents of liposomes for stabilizing liposomes when they are present in complex mixtures of adjuvants.