Sustained release of milrinone delivered via microparticles in a rodent model of myocardial infarction Hamood Al Kindi, MD, Arghya Paul, PhD, Zhipeng.

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Sustained release of milrinone delivered via microparticles in a rodent model of myocardial infarction Hamood Al Kindi, MD, Arghya Paul, PhD, Zhipeng You, PhD, Oleg Nepotchatykh, PhD, Adel Schwertani, PhD, Satya Prakash, PhD, Dominique Shum-Tim, MD The Journal of Thoracic and Cardiovascular Surgery Volume 148, Issue 5, Pages 2316-2324 (November 2014) DOI: 10.1016/j.jtcvs.2014.07.033 Copyright © 2014 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Characterization of microparticles. A, Transmission electron microscopy was used to obtain the size characterization. The polylactic-co-glycolic acid (PLGA) microparticles (MPs) measured ≈4 μm in diameter. Most microparticles were spherical in shape. B, Encapsulation efficiency using various milrinone (Mil)-PLGA concentrations. C, In vitro release kinetics of milrinone (Mil)-loaded PLGA microparticles over time. Mil-PLGA concentration of 1:20 was used in this study. The Journal of Thoracic and Cardiovascular Surgery 2014 148, 2316-2324DOI: (10.1016/j.jtcvs.2014.07.033) Copyright © 2014 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Hemodynamic measurements. Data presented as mean ± standard deviation. A, Graphs of left ventricular ejection fraction determined by 2-dimensional images. B, Graphs of percentage of fractional shortening determined by 2-dimensional images. C, Graphs of mean arterial pressure measurements. D, Graphs of heart rate measurements. *P < .05, group III versus groups I and II; ψP < .05, group III versus group I; **P < .05 group II versus group I. The Journal of Thoracic and Cardiovascular Surgery 2014 148, 2316-2324DOI: (10.1016/j.jtcvs.2014.07.033) Copyright © 2014 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Plasma cytokine levels for group I (empty microparticles), group II (milrinone), and group III (microparticles plus milrinone). A, Ratio of serum tumor necrosis factor (TNF)-α to interleukin-10 levels. *P < .05, group I versus groups II and III. B, Rat cytokine panel. A, upper, Representative array images shown. Lower, Profiles, created by quantifying dot densities, background-subtracted, and normalized to positive controls, are presented. Note the signal intensities of serum intercellular adhesion molecule (ICAM) and cytokine-induced neutrophil chemoattractant-1 (CINC-1) in group III were significantly less than in the other groups. Macrophage inflammatory protein-3α (MIP-3α) and vascular endothelial growth factor (VEGF) were absent in groups II and III. *P < .05, group III versus groups I and II; **P < .05, group II versus group I; ψP < .05, group I versus groups II and III. LIX, Lipopolysaccharide-induced CXC chemokine; RANTES, chemokine ligand-5; TIMP-1, tissue inhibitors of metalloproteinase-1; IL-10, interleukin 10. The Journal of Thoracic and Cardiovascular Surgery 2014 148, 2316-2324DOI: (10.1016/j.jtcvs.2014.07.033) Copyright © 2014 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 High-performance liquid chromatography of milrinone in rat plasma. A, Group I (empty microparticles); B, group II (milrinone); and C, group III (microparticles plus milrinone). D, The mean plasma milrinone level in all 3 groups at 24 hours after tail vein injection. SD, Standard deviation. The Journal of Thoracic and Cardiovascular Surgery 2014 148, 2316-2324DOI: (10.1016/j.jtcvs.2014.07.033) Copyright © 2014 The American Association for Thoracic Surgery Terms and Conditions