Quinone propionic acid‐based redox‐triggered polymer nanoparticles for drug delivery: Computational analysis and in vitro evaluation |
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| Authors: | Jungeun Bae Manal A. Nael Lingzhou Jiang Patrick TaeJoon Hwang Fakhri Mahdi Ho‐Wook Jun Wael M. Elshamy Yu‐Dong Zhou S. Narasimha Murthy Robert J. Doerksen Seongbong Jo |
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| Affiliation: | 1. Department of Pharmaceutics, School of Pharmacy, The University of Mississippi, University, Mississippi;2. Department of Medicinal Chemistry, School of Pharmacy, The University of Mississippi, University, Mississippi;3. Department of Biomedical Engineering, University of Alabama at Birmingham, 1825 University Boulevard, Birmingham, Alabama;4. Department of Pharmacognosy, School of Pharmacy, The University of Mississippi, University, Mississippi;5. Cancer Institute and Department of Biochemistry, University of Mississippi Medical Center, Jackson, Mississippi;6. Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, Mississippi |
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| Abstract: | Redox‐responsive polymers with pendant quinone propionic acid groups as a redox trigger were optimized by computational modeling to prepare efficient redox‐triggered polymer nanoparticles (NPs) for drug delivery. Lipophilicities at complete reduction of redox‐responsive polymers (<5000 Da) constructed with adipic acid and glutaric acid were remarkably reduced to range from ?6.29 to ?0.39 compared with nonreduced state (18.87–32.46), suggesting substantial polymer solubility reversal in water. Based on this hypothesis, redox‐responsive NPs were prepared from the synthesized polymers with paclitaxel as model cancer drug. The average size of paclitaxel‐loaded NPs was 249.8 nm and their reconstitutions were stable over eight weeks. In vitro drug release profiles demonstrated the NPs to release >80% of paclitaxel over 24 h at a simulated redox‐state compared with 26.5 to 41.2% release from the control. Cell viability studies revealed that the polymer was nontoxic and the NPs could release paclitaxel to suppress breast cancer cell growth. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40461. |
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| Keywords: | stimuli‐sensitive polymers drug delivery systems nanoparticles nanowires and nanocrystals applications polyesters |
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