Advanced functional carriers based on polyelectrolyte-liposome complexes

Pinguet, Camille; Plamper, Felix Alois (Thesis advisor); Pich, Andrij (Thesis advisor)

Aachen (2018, 2019)
Dissertation / PhD Thesis

Dissertation, RWTH Aachen University, 2018

Abstract

Liposomes are often used as container. In this work, we build complexes of liposomes to increase their carrier performance. Multiliposomal complexes are built from small unilamellar anionic liposomes and cationic polymers due to electrostatic interaction. Firstly, we propose a strategy to adjust the size of complexes made of liposomes, prepared from zwitterionic lipid 1,2-dioleoyl-sn-glycerol-3-phosphocholine DOPC and ionic lipid 1-palmitoyl-2-oleoyl-sn-glycerol-3-phospho-L-serine POPS and polycations. Hereby, the polycation is a quaternized poly(dimethylaminoethyl methacrylate), qPDMAEMA. The size of the complexes can be adjusted by the introduction of poly(ethylene oxide) PEO moieties and/or branching. The PEO block present in copolymer or miktoarms star-shaped polymers leads to formations of smaller complexes. Thereby the branching (both star-shaped polymers in this case) has the same effect. Secondly the liposomes are complexed with larger cationic vesicular interpolyelectrolyte complexes, so-called IPECsomes. The vesicular IPECsomes are formed upon mixing of an anionic polyelectrolyte and an excess of cationic-nonionic star-shaped polymer. The opening of the multicompartmental containers was triggered by help of a sodium chloride solution to open the IPECsomes and a surfactant, Triton X100, to open the liposomes. The dependency of obtained multi-liposomal complexes on the ratio of the differently charged vesicles and on the added salt is studied by electrophoretic mobility measurements and dynamic light scattering. The structure of the complexes is investigated by cryogenic transmission electron microscopy (cryo-TEM). Thirdly we propose a strategy to counteract the salt-driven disassembly of multi-liposomal complexes driven by electrostatic attraction of small unilamellar anionic and cationic polymers. The combined action of (qPDMAEMA100)3.1 and a nonionic star-shaped polymer (PEO12-b-PPO45)4, which is made of diblock copolymer arms uniting a poly(ethylene oxide) PEO inner block and a poly(propylene oxide) PPO terminal block, leads to a stabilization of these complexes against disintegration in saline solutions. Hereby, the insertion of the PPO blocks into (several) lipid bilayer domains provides an additional adhesive component to retain the structure of the complexes stable. Both polymers work synergistically, as the joint action still assures some membrane integrity, which is not seen for the mere (PEO12-b-PPO45)4 - liposome interaction alone.

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