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

ALVES, P.A; HUGO, A. A.; TYMCZYSZYN,E.E; FERREIRA, A.F; FAUSTO, R; PÉREZ, P.F; COHELO,J.F.J; SIMOES, P.N; GÓMEZ-ZAVAGLIA, A

Bucarest

Congreso; ROMPHYSCHEM 15; 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. To improve the deliver 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) was synthesized by ATRP using cholesteryl-2-bromoisobutyrate as initiator. CHO-PDMAEMA was incorporated into 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 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 and no toxicity. 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.