Synthesis of Cholesterol-Poly(N,N-Dimethylaminoethyl Methacrylate) and Preparation of Polymer-Liposome Complexes for Drug Delivery

ALVES, P., HUGO, A.A., TYMCZYSZYN, E.E. FERREIRA, A.F., FAUSTO R., PÉREZ, P.F., COELHO, J.F.J., SIMÕES, P.N. AND GÓMEZ ZAVAGLIA, A

Porto

Congreso; 2th International Chemical and Biological Engineering Conference Chempor 2014; 2014

Chempor

The attachment of functional polymers to liposomes by means of hydrophobic anchors has emerged as a strategy to prepare stimuli-responsive materials used as drug delivery systems. For this purpose, a polymer with an hydrophobic anchor (cholesterol) was prepared by Atom Transfer Radical Polymerization (ATRP). The chosen polymer was poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) due to its ability of responding to environment changes in temperature or pH. PDMAEMA is an amphiphilic molecule composed of methacrylate, a substituent containing poly(2-ethylacrylic acid), responsible for temperature or pH changes. The synthetized polymer was then incorporated into a lecithin liposomal formulation in order to obtain a polymer-liposome complex (PLC). Thermal characterization of the obtained PLCs was performed by DSC. Physicochemical characterization was carried out by determining the zeta potential, particle size distribution, and the release of a fluorescent dye (calcein) at different temperatures and pHs. The stability of the PLC was also evaluated along time after incubation at 4°C, -80 °C and freeze-drying. In vitro studies on Raw 264.7 and Caco-2/TC7 cells demonstrated an efficient incorporation of PLCs into the cells. No toxicity of the prepared PLCs was observed according to MTT assays. This work reports promising results regarding the development of stable liposomes with stimuli-responsive properties that can be loaded with therapeutic drugs. Three main characteristics were afforded by the presence of PDMAEMA in liposome formulation: stabilization at neutral pH, increased uptake by phagocytic and non-phagocytic cells and release of content in mild acidic conditions. Our findings may lead to the possibility of targeting active compounds to specific intracellular compartments, thus improving biological effects.