Stabilization of polymer lipid complexes prepared with lipids of lactic acid bacteria upon preservation and internalization into eukaryotic cells

ALVES PATRICIA; HUGO AYELEN; SZYMANOWSKI FELIPE; TYMCZYSZYN E. E.; PEREZ P.; COELHO J.F.J.; SIMÕES P.N.; GOMEZ ZAVAGLIA, A.

COLLOIDS AND SURFACES B-BIOINTERFACES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2014 vol. 123 p. 446 - 451

0927-7765

 Thephysicochemical characterization of polymer liposome complexes (PLCs) preparedwith lipids oflactic acid bacteria and poly(N,N-dimethylaminoethylmethacrylate) covalently bound to cholesterol(CHO-PDMAEMA) was carried out inan integrated approach, including their stability upon preservationandincorporation into eukaryotic cells.PLCs were prepared with differentpolymer:lipid molar ratios (0, 0.05 and 0.10). Zeta potential, particlesizedistribution and polydispersity index were determined. The optimal polymer:lipidratio and thestability of both bare liposomes and PLCs were evaluated at 37 °C and at different pHs, as well as afterstorage at 4 °C, -80 °C and freeze-dryingin the presence or absence of trehalose 250 mM. Internalizationof PLCs byeukaryotic cells was assessed to give a complete picture of thesystem.Incorporation of CHO-PDMAEMA onto bacterial lipids (ratio 0.05 and 0.10)led to stabilization at 37 °C and pH 7. A slight decrease of pH led to theirstrong destabilization. Bacteria PLCs showed to be more stablethan lecithin(LEC) PLCs (used for comparison) upon preservation at 4 and -80 °C. The harmfulnature ofthe preservation processes led to a strong decrease in the stabilityof PLCs, bacterial formulations beingmore stable than LEC PLCs. The addition oftrehalose to the suspension of liposomes stabilized LEC PLCand did not haveeffect on bacterial PLCs.In vitro studies on Raw 264.7 and Caco-2/TC7 cellsdemonstrated an efficient incorporation of PLCs intothe cells. Preparationswith higher stability were the ones that showed a better cell-uptake.The natureof the lipid composition is determinant for the stability of PLCs. Lipids fromlactic acidbacteria are composed of glycolipids and phospholipids likecardiolipin and phosphatidylglycerol. Thepresence of negatively charged lipidsstrongly improves the interaction with the positively charged CHO-PDMAEMA, thusstabilizing liposomes. In addition, glycolipids and phosphatidylglycerol act asintrinsicprotectants of PLCs upon preservation.This particular lipidcomposition of lactic acid bacteria makes them natural formulationspotentiallyuseful as drug delivery systems.