MEMBRANE-FUSION AND RUPTURE IN LIPOSOMES - EFFECT OF BIODEGRADABLE PH-SENSITIVE SURFACTANTS

Biodegradable pH-sensitive surfactants (BPS) are a unique family of ea sily metabolized compounds that demonstrate pH-dependent surface activ ity. These agents, in combination with other delivery systems, have de monstrated effects in enhancing transnucleic acid activity. The increa sed activity has been hypothesized to occur from a release of endosoma l contents. Simply, the BPS delivery system containing nucleic acids e nters the cell through an endocytotoic process. It encounters an acidi c pH and becomes surface active leading to defects in the endosomal me mbrane. In the current study, an in vitro model membrane was used to b etter understand the liposome defect mechanisms that BPS elicit. Using this system, it is shown that BPS can induce both liposome fusion and rupture depending upon the pH and mole ratio of BPS to membrane lipid s. Futhermore, liposome fusion induced by BPS was dependent on the tot al numbers of liposome particles while rupture was independent of inte racting liposome particles. The generated data indicate that BPS agent s act differently from other typical surface active agents and fuosgen ic compounds. Instead of facilitating membrane fusion through the hexa gonal II phase, BPS appeared to contribute and participate in the memb rane fusion at different stages.