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Paclitaxel-conjugated PEG and arginine-grafted bioreducible poly (disulfide amine) micelles for co-delivery of drug and gene
Authors:Kihoon Nam  Hye Yeong Nam  Pyung-Hwan Kim  Sung Wan Kim
Affiliation:Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
Abstract:We developed a paclitaxel-conjugated polymeric micelle, ABP-PEG(3.5k)-Paclitaxel (APP) consisting of poly (ethylene glycol) (PEG) and arginine-grafted poly (cystaminebisacrylamide-diaminohexane) (ABP) for the co-delivery of gene and drug. The APP polymer self-assembled into cationic polymeric micelles with a critical micelle concentration (CMC) value of approximately 0.062?mg/mL, which was determined from measurements of the UV absorption of pyrene. The micelles have an average size of about 3?nm and a zeta potential of about?+14?mV. Due to the positive surface charge, APP micelles formed polyplexes with plasmid DNA approximately 200?nm in diameter. The luciferase gene and mouse interleukin-12 (IL-12) gene was used to monitor gene delivery potency. APP polyplexes showed increased gene delivery efficiency and cellular uptake with higher anticancer potency than paclitaxel alone. These results demonstrate that an APP micelle-based delivery system is well suitable for the co-delivery of gene and drug.
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