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Pharmaceutics 2017, 9(1), 4; doi:10.3390/pharmaceutics9010004

Doxorubicin Delivery Using pH and Redox Dual-Responsive Hollow Nanocapsules with a Cationic Electrostatic Barrier

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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Author to whom correspondence should be addressed.
Academic Editor: Murali Mohan Yallapu
Received: 2 December 2016 / Revised: 23 December 2016 / Accepted: 26 December 2016 / Published: 30 December 2016
(This article belongs to the Special Issue Nanotechnology in Medical Therapeutic Formulations)
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Abstract

For the delivery of doxorubicin (DOX), pH and redox dual responsive hollow nanocapsules were prepared through the stabilization of polymer vesicles, which spontaneously formed from polyamidoamine dendron-poly(l-lysine) (PAMAM dendron-PLL), by the introduction of disulfide (SS) bonds between PLLs. The SS-bonded nanocapsules exhibited a very slow release of DOX under an extracellular environment because the cationic PLL membrane acted as an electrostatic barrier against the protonated DOX molecules. However, increasing the glutathione concentration to the intracellular level facilitated the immediate release of DOX through the collapse of nanocapsules by the spontaneous cleavage of SS bonds. SS-bonded nanocapsules also escaped from the endosome by the buffering effect of PAMAM dendrons, and DOX delivery into the cytoplasm was achieved. Furthermore, DOX molecules delivered by SS-bonded nanocapsules exhibited an effective in vitro anticancer effect to HeLa cells. View Full-Text
Keywords: hollow nanocapsules; doxorubicin; dual responsive; electrostatic barrier; drug delivery system; self-assembled polymers hollow nanocapsules; doxorubicin; dual responsive; electrostatic barrier; drug delivery system; self-assembled polymers
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Teranishi, R.; Matsuki, R.; Yuba, E.; Harada, A.; Kono, K. Doxorubicin Delivery Using pH and Redox Dual-Responsive Hollow Nanocapsules with a Cationic Electrostatic Barrier. Pharmaceutics 2017, 9, 4.

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