Nitric Oxide-Loaded Echogenic Liposomes for Nitric Oxide Delivery and Inhibition of Intimal Hyperplasia
Shao-Ling Huang, MD, PhD*,*,
Patrick H. Kee, MD, PhD*,
Hyunggun Kim, PhD*,
Melanie R. Moody, MS*,
Stephen M. Chrzanowski*,
Robert C. MacDonald, PhD and
David D. McPherson, MD*
* Division of Cardiology, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois
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Figure 1 NO Release Profile
Illustrated is the amount of released NO when pure NO (open circles) or a mixture of 20% NO with 80% Ar (closed circles) were encapsulated into the liposomes. NO = nitric oxide; NO/Ar-ELIP = nitric oxide/argon-containing liposomes; NO-ELIP = nitric oxide-containing liposomes.
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Figure 2 Cell Viability With NO-ELIP
Vascular smooth muscle cell viability at 4 h after differing amounts of NO/Ar (1:9)-containing liposomes. Viability was measured with the use of calcein AM. Abbreviations as in Figure 1.
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Figure 3 NO Delivery Into Cultured Vascular Smooth Muscle Cells
Cells were cultured in 48-well plates and incubated with NO/Ar (1:9)-saturated mannitol (left) or 30 µg of NO/Ar (1:9)-containing liposomes (right) for 10 min. The uptake of NO was expressed as nitrate and nitrite concentrations. Abbreviations as in Figure 1.
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Figure 4 Cellular Uptake of NO
Representative DAF-2DA fluorescence images of vascular smooth muscle cells treated with (A) NO/Ar-saturated mannitol solution in the absence of hemoglobin, (B) NO/Ar (1:9)-containing liposomes in the absence of hemoglobin, (C) NO/Ar (1:9)-saturated mannitol solution in the presence of hemoglobin, and (D) NO/Ar (1:9)-containing liposomes in the presence of hemoglobin. DAF-2DA = diaminofluorescein-2 diacetate; other abbreviations as in Figure 1.
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Figure 5 NO/Ar-ELIP Effect on Inhibition of Neointimal Hyperplasia
Representative histological sections of (A) normal common carotid artery (no balloon injury), (B) common carotid artery 14 days after balloon injury, (C) common carotid artery 14 days after balloon injury treated with Ar-ELIP, and (D) common carotid artery 14 days after balloon injury treated with NO/Ar (1:9)-containing liposomes (hematoxylin and eosin x400). Abbreviations as in Figure 1.
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Figure 6 Quantitation of Neointimal Hyperplasia
(A) Intima/media thickness ratio and (B) intimal area of injured common carotid arteries: control (left); treated with Ar-ELIP (middle); and treated with NO/Ar (1:9)-containing liposomes (right). Abbreviations as in Figure 1.
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