caa a22 4500 445313218 CHVBK 20180317142637.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s11095-011-0470-1 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0470-1 Polymer Micelles with Hydrazone-Ester Dual Linkers for Tunable Release of Dexamethasone [Elektronische Daten] [Melissa Howard, Andrei Ponta, Allison Eckman, Michael Jay, Younsoo Bae] ABSTRACT: Purpose: To develop polymer micelles for the tunable release of Dexamethasone (DEX) in tumors. Methods: DEX was conjugated to poly(ethylene glycol)-poly(aspartate) block copolymers using hydrazone, ester, or hydrazone-ester dual linkers. Ketonic acids containing 3, 4, and 5 methylene groups were used as spacers to separate the dual linkers. Polymer micelles from the DEX-conjugated polymers were tested for drug release at different pH values and carboxylesterase activity levels. Results: DLS measurements and 1H-NMR analysis confirmed all DEX-loaded micelles were <100nm with core-shell structure. Single linker micelles appeared unsuitable to release DEX preferentially in acidic tumor tissues. Hydrazone linkages between DEX and polymers were non-degradable at both pH 7.4 and 5.0. Ester linkages stable at pH 5.0 were unstable at pH 7.4. Hydrazone-ester dual linkers suppressed DEX release at pH 7.4 while accelerating drug release at pH 5.0. DEX release decreased at pH 5.0 as the length of ketonic acid increased but was independent of spacer length at pH 7.4. Dual linker micelles were stable in the presence of carboxylesterases, suggesting DEX release was primarily due to pH-dependent hydrolysis. Conclusion: Tunable release of DEX was achieved using pH-sensitive polymer micelles with hydrazone-ester dual linkers. Springer Science+Business Media, LLC, 2011 dexamethasone nationallicence drug delivery nationallicence ester nationallicence hydrazone nationallicence polymer micelles nationallicence Howard Melissa Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, 40536-0596, Lexington, KY, USA aut Ponta Andrei Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, 40536-0596, Lexington, KY, USA aut Eckman Allison Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, 40536-0596, Lexington, KY, USA aut Jay Michael Division of Molecular Pharmaceutics, Eshelman School of Pharmacy Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA aut Bae Younsoo Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, 40536-0596, Lexington, KY, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/10(2011-10-01), 2435-2446 0724-8741 28:10<2435 2011 28 11095 https://doi.org/10.1007/s11095-011-0470-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0470-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Howard Melissa Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, 40536-0596, Lexington, KY, USA aut NATIONALLICENCE 700 1- Ponta Andrei Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, 40536-0596, Lexington, KY, USA aut NATIONALLICENCE 700 1- Eckman Allison Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, 40536-0596, Lexington, KY, USA aut NATIONALLICENCE 700 1- Jay Michael Division of Molecular Pharmaceutics, Eshelman School of Pharmacy Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA aut NATIONALLICENCE 700 1- Bae Younsoo Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, 40536-0596, Lexington, KY, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/10(2011-10-01), 2435-2446 0724-8741 28:10<2435 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer