Cyclodextrin-Based Star-Like Amphiphilic Cationic Polymer as a Potential Pharmaceutical Carrier in Macrophages

Effective delivery of therapeutic genes or small molecular drugs into macrophages is important for cell based immune therapy, but it remains a challenge due to the intracellular reactive oxygen species and endosomal degradation of therapeutics inside immune cells. In this report, the star-like amphiphilic biocompatible β-cyclodextrin-graft-(poly(ε-caprolactone)-block-poly(2-(dimethylamino) ethyl methacrylate)_x (β-CD-g-(PCL-b-PDMAEMA)_x ) copolymer, consisting of a biocompatible cyclodextrin core, hydrophobic poly(ε-caprolactone) PCL segments and hydrophilic PDMAEMA blocks with positive charge, is optimized to achieve high efficiency gene transfection with enhanced stability, due to the micelle formation by hydrophobic PCL segments. In comparison with lipofetamine, a currently popular nonviral gene carrier, β-CD-g-(PCL-b-PDMAEMA)_x copolymer, shows better transfection efficiency of plasmid desoxyribose nucleic acid in RAW264.7 macrophages. More interestingly, this delivery platform by β-CD-g-(PCL-b-PDMAEMA)_x not only shows low toxicity but also better dexamethasone delivery efficiency, which might indicate its great potential in immunotherapy.