Effect of cholesterol-poly(N,N-dimethylaminoethyl methacrylate) on the properties of stimuli-responsive polymer liposome complexes

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

Congreso; European Polymer Congress; 2013

Liposomes are attractive materials for drug delivery because of their biocompatibility, non-immunogenicity, non-toxicity, and ability to entrap both hydrophilic and hydrophobic compounds. However, for the delivery process to be efficient, they should be able to entrap drugs and release them at the target cell, which in several cases is still an unsolved problem. To improve the leakage process, different approaches have been employed. Among them, the design of stimuli-sensitive liposomes capable of releasing their contents in response to environmental changes (e.g.: temperature, pH) has been described as a promising approach. The development of new polymer-liposome complexes (PLCs) as delivery systems is the key issue of this work. Poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) with low molecular weight and narrow polydispersity was synthesized by Atom Transfer Radical Polymerization (ATRP) using cholesteryl-2-bromoisobutyrate as initiator. CHO-PDMAEMA was incorporated in the preparation of lecithin liposomes (LEC) to obtain PLCs. Physicochemical characterization of PLCs was carried out by determining the zeta potential, particle size distribution, and the release of fluorescent dyes (carboxyfluorescein -CF- and calcein) at different temperatures and pHs. 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. In summary, the main achievements of this work are: a) novel synthesis of CHO-PDMAEMA by ATRP, b) stabilization of LEC by incorporation of CHO-PDMAEMA at neutral pH and destabilization upon slight changes of pH, c) efficient uptake of LEC_CHO-PDs by phagocytic and non-phagocytic eukaryotic cells.