Magnetic field responsive drug release from magnetoliposomes in biological fluids

Abstract

The final fate of nano-scaled drug delivery systems into the body is highly affected by their interaction with proteins in biological fluids (serum, plasma, etc.). Nanocarriers dispersed in biological fluids bear a protein “corona” that covers their surface. Thus, it is extremely important to evaluate the drug release efficiency also in the biological environment where protein-nanocarrier complexes are formed. The purpose of this work is to determine how drug release from lipid vesicle carriers is influenced by the interaction with serum proteins, highlighting the importance to test the effectiveness of such systems in the biological milieu. In particular, this paper describes the magnetically triggered release behaviour of magnetoliposomes (MLs) dispersed both in aqueous physiological buffer and in bovine serum at two different concentrations (10% and 55% v/v) upon exposure to a low-frequency alternating magnetic field (LF-AMF). We studied the release from MLs loaded with two types of magnetic nanoparticles (MNPs): citrate coated Fe₃O₄ and oleic acid coated γ-Fe₂O₃. The permeability in the above-mentioned fluids was evaluated in terms of the fluorescence self-quenching of carboxyfluorescein (CF) entrapped inside the liposome aqueous pool. The results showed a strong reduction of the release in biological fluids, in particular at high serum concentration. We related this decrease to the formation of protein-liposome complexes that, under LF-AMF exposure, are subjected to destabilization and tend to form aggregates. Our results clearly highlight the importance of testing the release efficiency of self-assembled drug delivery systems in biological fluids, in order to understand their behaviour in the presence of proteins and biomolecules.