pH-sensitive double-hydrophilic block copolymer micelles for biological applications.

In the recent years, double-hydrophilic block copolymer (DHBC) micelles have appeared as potential vectors for pharmaceutical applications due to their simple preparation method in aqueous solvent. The present study aims at underscoring the strategy for the choice of the partners in the formulation of DHBC micelles presenting a good stability in physiological conditions (pH 7.4, 0.15 mol/L NaCl) and a pH-sensitivity allowing their disassembly at pH 5. Using light scattering and Laser-Doppler electrophoresis, micelles of polymethacrylic acid-b-polyethylene oxide complexing either poly-l-lysine (PLL) or an oligochitosan were characterised. Whatever the polyamine counter-polyion considered, the micelles were perfectly formed for an amine/methacrylic acid molar charge ratio of one. They were characterised by a hydrodynamic diameter of 28 nm for PLL and 60 nm for oligochitosan and by a neutral zeta potential. The stability study as a function of the pH and of the ionic strength revealed different behaviours. Oligochitosan micelles were stable until pH 7 and unstable at 0.15 mol/L NaCl. On the contrary, PLL micelles were stable in physiological conditions and disassembled at pH 5. As a conclusion, the choice of the partners to formulate double-hydrophilic block copolymer based-micelles is strategic in order to obtain well-adapted vectors applied to the pharmaceutical field.