Stable positively charged liposome during long-term storage.

Abstract

The effect of taurine, as an isotonic solute, and of benzalkonium chloride (BZC), as a positive membrane component, on the long-term stability of liposomal suspensions was investigated by measuring surface potential. The surface potential, which introduced electrostatic repulsion to liposomes against aggregation, increased dose-dependently with the addition of BZC, which gave a positive charge. However, a further addition of BZC caused unexpected aggregation during storage, so the optimum addition of BZC was defined. On the other hand, taurine, which forms a zwitter ion in an aqueous solution, did not reduce the surface potential, suggesting that taurine is of possible utility as an isotonic solute. As the result of stability testing, the liposomal system using taurine and BZC was stable against aggregation during 6 months at 40 degrees C. We were successful in developing a stable, positively charged liposomal system during long-term storage, and our liposomal system is believed to be of wide utility as a drug carrier for therapeutic drugs applied topically to negatively charged mucosal tissues. We applied the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory to estimate the colloidal stability of liposomes. As a result of stability testing, positively charged liposomes had a good correlation between maximum total repulsive energy (VT(max)/kT) between two liposome particles and colloidal stability, suggesting that the VT(max)/kT value is useful for estimating stability and for designing liposomal preparations containing some ionic substances.