Intracellular Environment-Responsive Stabilization of Polymer Vesicles Formed from Head-Tail Type Polycations Composed of a Polyamidoamine Dendron and PolyL-lysineReportar como inadecuado




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Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan





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Abstract For the development of effective drug carriers, nanocapsules that respond to micro-environmental changes including a decrease in pH and a reductive environment were prepared by the stabilization of polymer vesicles formed from head-tail type polycations, composed of a polyamidoamine dendron head and a polyL-lysine tail PAMAM dendron-PLL, through the introduction of disulfide bonds between the PLL tails. Disulfide bonds were successfully introduced through the reaction of Lys residues in the PAMAM dendron-PLL polymer vesicles with 2-iminothiolane. The stabilization of PAMAM dendron-PLL polymer vesicles was confirmed by dynamic light scattering measurements. In acid-base titration experiments, nanocapsules cross-linked by disulfide bonds had a buffering effect during the cellular uptake process. The PAMAM dendron-PLL nanocapsules were used to incorporate the fluorescent dyes rhodamine 6G and fluorescein as a drug model. Cationic rhodamine 6G was generally not released from the nanocapsules because of the electrostatic barrier of the PLL membrane. However, the nanocapsules were destabilized at high glutathione concentrations corresponding to intracellular concentrations. Rhodamine 6G was immediately released from the nanocapsules because of destabilization upon the cleavage of disulfide bonds. This release of rhodamine 6G from the nanocapsules was also observed in HeLa cells by laser confocal microscopy. View Full-Text

Keywords: nanocapsule; drug delivery system; disulfide bond; glutathione; head-tail type polycation nanocapsule; drug delivery system; disulfide bond; glutathione; head-tail type polycation





Autor: Atsushi Harada * , Ryota Matsuki, Shin-ichi Ichimura, Eiji Yuba and Kenji Kono

Fuente: http://mdpi.com/



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