Nitric Oxide-Loaded Echogenic Liposomes for Nitric Oxide Delivery and Inhibition of Intimal Hyperplasia

Huang, Shaoling; Kee, Patrick; Kim, Hyunggun; Moody, Melanie R.; Chrzanowski, Stephen M.; MacDonald, Robert C.; McPherson, David D.

doi:10.1016/j.jacc.2009.04.039

Cited by 106 publications

(94 citation statements)

References 25 publications

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“…46,55 In this study, vascular relaxation was triggered from NOBLs with pulsed ultrasound at a peak-to-peak acoustic pressure amplitude of 0.34 MPa. Despite the detection of strong cavitation at this acoustic pressure, the precise mechanism of NO release and delivery remains unclear.…”

Section: Ultrasound Exposure and Cavitationmentioning

confidence: 99%

Pulsed ultrasound enhances the delivery of nitric oxide from bubble liposomes to ex vivo porcine carotid tissue

Sutton¹,

Raymond²,

Verleye³

et al. 2014

IJN

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Ultrasound-mediated drug delivery is a novel technique for enhancing the penetration of drugs into diseased tissue beds noninvasively. By encapsulating drugs into microsized and nanosized liposomes, the therapeutic can be shielded from degradation within the vasculature until delivery to a target site by ultrasound exposure. Traditional in vitro or ex vivo techniques to quantify this delivery profile include optical approaches, cell culture, and electrophysiology. Here, we demonstrate an approach to characterize the degree of nitric oxide (NO) delivery to porcine carotid tissue by direct measurement of ex vivo vascular tone. An ex vivo perfusion model was adapted to assess ultrasound-mediated delivery of NO. This potent vasodilator was coencapsulated with inert octafluoropropane gas to produce acoustically active bubble liposomes. Porcine carotid arteries were excised post mortem and mounted in a physiologic buffer solution. Vascular tone was assessed in real time by coupling the artery to an isometric force transducer. NO-loaded bubble liposomes were infused into the lumen of the artery, which was exposed to 1 MHz pulsed ultrasound at a peak-to-peak acoustic pressure amplitude of 0.34 MPa. Acoustic cavitation emissions were monitored passively. Changes in vascular tone were measured and compared with control and sham NO bubble liposome exposures. Our results demonstrate that ultrasound-triggered NO release from bubble liposomes induces potent vasorelaxation within porcine carotid arteries (maximal relaxation 31%±8%), which was significantly stronger than vasorelaxation due to NO release from bubble liposomes in the absence of ultrasound (maximal relaxation 7%±3%), and comparable with relaxation due to 12 μM sodium nitroprusside infusions (maximal relaxation 32%±3%). This approach is a valuable mechanistic tool for assessing the extent of drug release and delivery to the vasculature caused by ultrasound.

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Section: Ultrasound Exposure and Cavitationmentioning

confidence: 99%

Pulsed ultrasound enhances the delivery of nitric oxide from bubble liposomes to ex vivo porcine carotid tissue

Sutton¹,

Raymond²,

Verleye³

et al. 2014

IJN

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“…Huang et al 83 evaluated the synthetic dimyristoylphosphatidylcholine liposomal formulation of this antiproliferative agent in vitro using smooth-muscle cells and found a sevenfold higher uptake of nitric oxide-argon liposomes compared to nonencapsulated nitric oxide. Using an in vivo model of hyperplasia based on balloon-injured carotid arteries in rabbits, the liposomes promoted regression of lesions in cholesterol-fed rabbits, demonstrating attenuated hyperplasic development of smooth-muscle cells and reduced arterial wall thickening by 41%.…”

Section: Arterial Intimal Hyperplasia and In-stent Restenosismentioning

confidence: 99%

The physiology of cardiovascular disease and innovative liposomal platforms for therapy

Ruiz–Esparza

Flores‐Arredondo

Segura‐Ibarra

et al. 2013

IJN

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Heart disease remains the major cause of death in males and females, emphasizing the need for novel strategies to improve patient treatment and survival. A therapeutic approach, still in its infancy, is the development of site-specific drug-delivery systems. Nanoparticlebased delivery systems, such as liposomes, have evolved into robust platforms for site-specific delivery of therapeutics. In this review, the clinical impact of cardiovascular disease and the pathophysiology of different subsets of the disease are described. Potential pathological targets for therapy are introduced, and promising advances in nanotherapeutic cardiovascular applications involving liposomal platforms are presented.

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“…A mixture (10 mL) of NO (Specialty Gases of America Inc, Toledo, OH, USA) and argon (Matheson Tri-Gas, Houston, TX, USA) at a ratio of 1:9 was purified by bubbling through deoxygenated 5 M NaOH. 25 The gaseous mixture of NO and argon was injected into the glass vial through a Teflon rubber septum using a 12 mL syringe attached to a 27G × 0.5 inch needle. The pressurized liposomal dispersion was frozen at −70°C for 30 minutes.…”

Section: Preparation Of No-elipmentioning

confidence: 99%

“…20 We have recently developed a novel methodology to encapsulate bioactive gases replacing air into our liposomal nanovehicles. [21][22][23][24][25] Coencapsulation of NO with argon enabled us to adjust the amount of encapsulated NO. A total of 10 µL of gas was encapsulated into 1 mg of liposomes.…”

Section: Introductionmentioning

confidence: 99%

“…We have demonstrated that both pulsed diagnostic ultrasound and continuous ultrasound can be utilized to enhance therapeutic release from ELIP. [25][26][27] In this study, we evaluated NO-ELIP for ultrasoundfacilitated site-specific NO delivery to produce vasodilation affecting vasospasm following subarachnoid hemorrhage. We investigated the vasodilative effects of NO released from NO-ELIP following ultrasound exposure in in vitro, ex vivo, and in vivo models.…”

Section: Introductionmentioning

confidence: 99%

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Nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage

Kim¹,

Britton²,

Peng³

et al. 2013

IJN

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Delayed cerebral vasospasm following subarachnoid hemorrhage causes severe ischemic neurologic deficits leading to permanent neurologic dysfunction or death. Reduced intravascular and perivascular nitric oxide (NO) availability is a primary pathophysiology of cerebral vasospasm. In this study, we evaluated NO-loaded echogenic liposomes (NO-ELIP) for ultrasound-facilitated NO delivery to produce vasodilation for treatment of vasospasm following subarachnoid hemorrhage. We investigated the vasodilative effects of NO released from NO-ELIP both ex vivo and in vivo. Liposomes containing phospholipids and cholesterol were prepared, and NO was encapsulated. The encapsulation and release of NO from NO-ELIP were determined by the syringe/vacuum method and ultrasound imaging. The ex vivo vasodilative effect of NO-ELIP was investigated using rabbit carotid arteries. Arterial vasodilation was clearly observed with NO-ELIP exposed to Doppler ultrasound whereas there was little vasodilative effect without exposure to Doppler ultrasound in the presence of red blood cells. Penetration of NO into the arterial wall was determined by fluorescent microscopy. The vasodilative effects of intravenously administered NO-ELIP in vivo were determined in a rat subarachnoid hemorrhage model. NO-ELIP with ultrasound activation over the carotid artery demonstrated effective arterial vasodilation in vivo resulting in improved neurologic function. This novel methodology for ultrasound-controlled delivery of NO has the potential for therapeutic treatment of vasospasm following subarachnoid hemorrhage. This ultrasound-controlled release strategy provides a new avenue for targeted bioactive gas and therapeutic delivery for improved stroke treatment.

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Nitric Oxide-Loaded Echogenic Liposomes for Nitric Oxide Delivery and Inhibition of Intimal Hyperplasia

Cited by 106 publications

References 25 publications

Pulsed ultrasound enhances the delivery of nitric oxide from bubble liposomes to ex vivo porcine carotid tissue

Pulsed ultrasound enhances the delivery of nitric oxide from bubble liposomes to ex vivo porcine carotid tissue

The physiology of cardiovascular disease and innovative liposomal platforms for therapy

Nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage

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