Abstract
The effects of surface modifications on liposomes using a library of arginine derivatives for improved drug delivery were examined. Both unmodified and modified liposomes were tested for their drug delivery properties and propensity for internalization by macrophages. All materials were characterized by dynamic light scattering (DLS) and zeta potential. The resulting liposomes were able to encapsulate doxorubicin with a loading efficiency greater than 90% and cumulative releases of less than 15% after 144 h. The internalization of these particles was examined by loading the liposomes with fluorescein or doxorubicin to test internalization through fluorescence level and half maximal inhibitory concentration (IC50), respectively. RAW 264.7 macrophages were activated with lipopolysaccharide (LPS) or interleukin-4 (IL-4) to induce M1- or M2-like phenotypes. Naïve macrophages were also studied. Most modified liposomes enhanced the cytotoxicity of doxorubicin compared to unmodified liposomes. Macrophage phenotype was also observed to influence the cytotoxicity of doxorubicin entrapped in modified liposomes, with some samples enhancing the cytotoxicity in LPS stimulated macrophages and some enhancing toxicity in IL-4 stimulated cells.
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