Sequential delivery of therapeutic agents using a rationally designed disulfide-linked glycolipid-like nanocarrier
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Yingwen Hu1,2, Na Liu1, Bolin Cheng1, Yanan Tan1, Lijuan Wen1, Hong Yuan1, Fuqiang Hu1
1Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, People’s Republic of China
2Department of Chemistry, Purdue University, West Lafayette, IN 47907, United States of America
Fuqiang Hu, email: firstname.lastname@example.org
Keywords: co-delivery, sequential, combined therapy, redox-responsive, drug resistance
Received: January 20, 2016 Accepted: October 13, 2016 Published: November 04, 2016
Usage of combination therapies to deliver multiple therapeutics to increase treatment efficacy has shown promising results in the clinic. In an effort to maximize the synergistic effect of co-delivery of a drug and siRNA, we have developed a time-dependent sequential drug delivery system (DDS) based on a disulfide-linked chitosan-based nanocarrier (CS-ss-SA) for the co-delivery of paclitaxel (PTX) and Bcl-2 specific siRNA (siBcl-2). This CS-ss-SA nanocarrier is able to transport both drug and siRNA by entrapment of PTX and adsorption of siRNA on the shell by electrostatic attraction. We show that this nanocarrier transports siRNA into tumor cells via its glycolipid-like spatial structure and releases a hydrophobic model drug, Nile Red 8-11 h later. Next, when siRNA and the hydrophobic drug PTX were co-delivered to tumor cells, a synergistic effect was observed in both cell cycle arrest and cell viability. Ultimately, the co-delivery of PTX and siBcl-2 by CS-ss-SA may prove to be more efficacious and may even help overcome drug resistance.
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