Efficient electroporation of liposomes doped with pore stabilizing nisin

Context: Liposomes have a long history as passive and active drug carriers. Recently, a few methods have been realized to control the release from liposomes, including heating, ultrasound and laser. Objective: We report on a new approach to drive release from liposomes using electric fields. Materials and methods: Liposomes were manufactured containing a high concentration of (quenched) 5-6 carboxyfluorescein dye. Nisin, a well-known amphiphilic peptide lantibiotic that works by stabilizing pores formed in cell membranes, was mixed in solution inside or outside the liposomes. The liposomes were then electroporated using a range of voltages, and assayed for increases in fluorescence due to release of dye. Release was measured against positive and negative controls, with positive control release driven by a strong detergent. Results: Our results demonstrate that the addition of nisin significantly reduces the electric field required to release the contents of liposomes, from 2000 V/m to approximately 200 V/m. This result proves that, in principle, electroporation (EP) of liposomes doped with small amounts of amphiphilic pore stabilizing peptides may be a practical means to drive release of liposomal contents in vivo. Conclusion: Drug delivery from liposomes doped with amphiphilic peptides using EP is feasible. This technique could be developed into a potent adjuvant to tumor ablation using irreversible EP.