Evaluation of lipid of lactic acid bacteria for the stabilization of polymer‐liposome complexes with potential applications in drug delivery

HUGO, A. A.; ALVES, P.; TYMCZYSZYN, E.; SZYMANOWSKI, F.; PÉREZ, P. F.; COELHO, J. F. J.; SIMÕES, P. N. AND GOMEZ‐ZAVAGLIA, A.

Simposio; IV Simposio Internacional de Bacterias Lácticas; 2013

Liposomes are attractive materials for drug delivery and the lipid composition is responsible for the stabilization of liposome formulations. Bacterial lipids are mainly found in cell membranes and have a crucial role in stabilizing the membrane structure when cells are exposed to stress processes. The lipid composition of lactic acid bacteria includes cardiolipin and phosphatidylglycerol as main phospholipids and three different glycolipids. In addition, the unsaturated/saturated fatty acids ratio is also related with the stability to different kinds of stresses involving membrane damage (i.e.: freeze‐thawing, lyophilization). Thus, lipids from lactic acid bacteria represent natural formulations that may be potentially useful in drug delivery. The internalization of liposomes in the tissues and the action on drug entrapped in target cells can be favoured by the incorporation of pHsensitive polymer, such us Poly(2‐(dimethylamino)ethyl methacrylate) (PDMAEMA). With this background, the aim of this work was to study the stability of liposomes formed by a lipid extract of Lactobacillus delbrueckii subsp. lactis CIDCA 133 with different concentrations of PDMAEMA. The leakage at different pHs was evaluated using calcein entrapped liposomes. The formulation containing 5 and 10% of PDMAEMA showed highest stability at pH 7 and 37°C. When pH decreased to 5, a rapid release of calcein was observed. Similar results were found in lecithin/PDMAEMA liposomes. Liposome formulations were preserved at 4°C, frozen at ‐20 and 80°C and freeze‐dried. 250 mM Trehalose was used as cryoportectant agent in all cases. After freeze‐drying, liposome formulations containing bacterial lipids showed higher stability than those prepared with lecithin. The presence of trehalose in the medium increased the stability of lipid formulation containing bacterial lipids and PDMAEMA 5% along time. In vitro studies on Raw 264.7 and Caco‐2/TC7 cells demonstrated an efficient incorporation of liposomes into the cells. These results substantiate the efficiency of PDMAEMA incorporated onto bacterial lipids liposomes to assist for the release of the liposome content in mildly acidic environments, like those found in early endosomes where pH is slightly lower than the physiologic. In summary, the main achievement of this work was the utilization of bacterial lipids from Lactobacillus delbrueckii subsp. lactis in the formulation of polymer‐liposomes with noticeable advantages on the stabilization respect to lecithin based formulations.