pH-sensitive vesicles containing a lipidic β-amino acid with two hydrophobic chains

The lipidic P-amino acid 2-(aminomethyl)-2-pentadecylheptadecanoic acid (1) was synthesized via the alkylation of the C(alpha)-atom of fully protected beta-alanine. Mixed large unilamellar vesicles with a diameter between 100 and 200 nm containing POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and 1 at a molar ratio of 9: 1 were prepared and found to have a surface charge which is dependent on pH. At slightly acidic pH, the vesicles were positively charged, and at alkaline pH negatively charged. Dynamic light scattering, zeta potential, and cryo-transmission electron-microscopy measurements indicated that the mixed vesicles fused at pH 4 - 5 with negatively charged mixed vesicles composed of POPC and POPG (9.8: 1, molar ratio), POPG being 1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)].