Reinforcement of Polymeric Nanoassemblies for Ultra-High Drug Loadings, Modulation of Stiffness and Release Kinetics, and Sustained Therapeutic Efficacy
- UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
- Luis A. Mejia Cruz (Creator)
- Nicholas Oberlies, Patricia A. Sullivan Distinguished Professor of Chemistry (Creator)
- Daniel A. Todd (Creator)
- Institution
- The University of North Carolina at Greensboro (UNCG )
- Web Site: http://library.uncg.edu/
Abstract: The optimization of current polymeric nanoparticle therapies is restricted by low drug loadings and limited tunability of core properties. To overcome these shortcomings, a novel self-association approach is utilized to fabricate a dual-loaded poly(1,2-glycerol carbonate)-graft-succinic acid-paclitaxel (PGC-PTX) conjugate nanoparticle (NP) in which the physical entrapment of free paclitaxel (PTX) affords unprecedented ultra-high drug loadings >100 wt%, modulation of mechanical stiffness, and tunable release kinetics. Despite high incorporation of free PTX (up to 50 wt%), the dual-loaded PGC-PTX nanocarriers (i.e., PGC-PTX + PTX NPs) exhibit controlled and sustained drug release over 15 days, without burst release effects. Importantly, optimization of drug/material efficiency concomitantly affords improved in vitro efficacy. In vivo, PGC-PTX + PTX NPs are safely administered at doses exceeding the median lethal dose of standard PTX, while a single high dose significantly extends survival relative to weekly PTX administrations in a murine model of peritoneal carcinomatosis.
Reinforcement of Polymeric Nanoassemblies for Ultra-High Drug Loadings, Modulation of Stiffness and Release Kinetics, and Sustained Therapeutic Efficacy
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Created on 2/8/2019
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Additional Information
- Publication
- Nanoscale, 10, 8360-8366
- Language: English
- Date: 2018
- Keywords
- polymeric nanoassemblies, nanocarriers, paclitaxel (PTX), drug loadings