Stability evaluation of polymer-liposome complexes for drug delivery systems prepared with bacterial lipids

ALVES, P.A; HUGO, A. A.; TYMCZYSZYN,E.E; SZYMANOWSKI, F; PÉREZ, P.F; COHELO,J.F.J; SIMOES, P.N; GÓMEZ-ZAVAGLIA, A

Porto

Congreso; 12th International Chemical and Biological Engineering Conference. CHEMPOR.; 2014

The physicochemical characterization of polymer liposome complexes (PLCs) prepared with lipids of lactic acid bacteria and cholesterol covalently bound to poly(N,N-dimethylaminoethyl methacrylate) (CHO-PDMAEMA) was carried out in an integrated approach including their stability upon preservation and incorporation into eukaryotic cells. PLCs were prepared with different polymer:lipid molar ratios (0, 5 and 10). Zeta potential, particle size distribution and polydispersity index were determined. The optimal polymer:lipid ratio and the stability of both bare liposomes and PLCs were evaluated at 37°C and at different pHs, as well as after preservation at 4°C, ?80°C and freeze-drying in the presence or absence of trehalose 250 mM. Internalization of PLCs by eukaryotic cells was assessed to give a complete picture of the system. Incorporation of CHO-PDMAEMA onto bacterial lipids (ratio 5 and 10) led to stabilization at 37°C and pH 7. A slight decrease in pH strongly destabilized them. Bacteria PLCs showed to be more stable than lecithin (LEC) PLCs (used for comparison) upon preservation at 4 and ?80°C. The harmful nature of the treatments led to a strong decrease in the stability of PLCs, bacterial formulations being more stable than LEC PLCs. The addition of trehalose stabilized LEC PLC and did not have effect on bacterial PLCs. In vitro studies on Raw 264.7 and Caco-2/TC7 cells demonstrated an efficient incorporation of PLCs into the cells, preparations with higher stability being better incorporated. The nature of lipid composition is determinant for the stability of PLCs. Lipids from lactic acid bacteria are composed of glycolipids and phospholipids like cardiolipin and phosphatidylglycerol. The presence of negatively charged lipids strongly facilitates the interaction with the positively charged CHO-PDMAEMA, thus stabilizing liposomes. In addition, glycolipids and phosphatidylglycerol act as intrinsic protectants of PLCs upon preservation. This particular composition of lipids from lactic acid bacteria makes them natural formulations potentially useful as drug delivery systems.