Physical correlates of the ultrasonic reflectivity of lipid dispersions suitable as diagnostic contrast agents

Huang, Shihai; Hamilton, Andrew J.; Pozharski, Edwin; Nagaraj, Ashwin; Klegerman, Melvin E.; McPherson, David D.; MacDonald, Robert C.

doi:10.1016/s0301-5629(01)00512-9

Cited by 85 publications

(85 citation statements)

References 33 publications

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“…Trehalose, which functions as a cryoprotectant by favoring glass formation rather than crystallization (either of itself or of the water) supported much less echogenicity than did mannitol. Mannitol is rather distinctive among sugars in readily crystallizing out of solution upon cooling and we previously found that freezing a mannitol solution inflicts damage upon liposomes (Huang et al 2002). It may be that such sites of damage provide gas bubble nucleation loci; this would be consistent with a hypothesis that similar interfaces are the preferred site of nucleation of nitrogen bubbles in decompression sickness which can affect divers (Craig et al 1996) Why is echogencity low when samples are thawed prior to reducing the pressure back to ambient pressure?…”

Section: Discussionmentioning

confidence: 61%

“…The amount of incorporated gas was determined using a previously described method (Huang et al 2002). Briefly, a 0.8-1 ml sample containing 5 mg lipid/ml is put into a 10-mL disposable syringe.…”

Section: Measurement Of the Amount Of Gas Into Lipid Dispersionsmentioning

confidence: 99%

“…They were then imaged with a 20-MHz high-frequency intravascular ultrasound image catheter, as previously described (Huang et al 2002). Images were recorded onto videotape, subsequently digitalized and computer analyzed in terms of a 0-256 mean gray scale value (MGSV) of the entire image.…”

Section: Ultrasound Imagingmentioning

confidence: 99%

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A Method to Co-Encapsulate Gas and Drugs in Liposomes for Ultrasound-Controlled Drug Delivery

Huang

McPherson

MacDonald

2008

Ultrasound in Medicine & Biology

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A novel method for the facile production of gas-containing liposomes with simultaneous drug encapsulation is described. Liposomes of phospholipid and cholesterol were prepared by conventional procedures of hydrating the lipid film, sonicating, freezing and thawing. A single, but critical modification of this procedure generates liposomes that contain gas (air, perfluorocarbon, argon); after sonication, the lipid is placed under pressure with the gas of interest. After equilibration, the sample is frozen. The pressure is then reduced to atmospheric and the suspension thawed. This procedure leads to entrapment of air in amounts up to 10% by volume by lipid dispersions at moderate (10mg/ml) concentrations of lipids. The amount of gas encapsulated increases with gas pressure and lipid concentration. Utilizing 0.32 M mannitol to provide an aqueous phase with physiological osmolarity, 1, 3, 6 or 9 atm of pressure was applied to 4 mg of lipid. This led to encapsulation of 10, 15, 20, and 30 l of gas in a total of 400 l of liposome dispersion (10mg lipids/ml), respectively. The mechanism for gas encapsulation presumably depends upon the fact that air (predominantly nitrogen and oxygen), like most solutes, dissolves poorly in ice and is excluded from the ice that forms during freezing. The excluded air then comes out of solution as air pockets that are stabilized in some form by a lipid coating. The presence of air in these preparations sensitizes them to ultrasound (1MHz, 8 W/cm 2 ,10 second) such that up to half of their aqueous contents (which could be a water soluble drug) can be released by short (10 s) applications of ultrasound. Both diagnostic and therapeutic applications of the method are conceivable.

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Section: Discussionmentioning

confidence: 61%

Section: Measurement Of the Amount Of Gas Into Lipid Dispersionsmentioning

confidence: 99%

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A Method to Co-Encapsulate Gas and Drugs in Liposomes for Ultrasound-Controlled Drug Delivery

Huang

McPherson

MacDonald

2008

Ultrasound in Medicine & Biology

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“…In vitro ultrasound-triggered NO release from NO-elIP Encapsulation and release of NO from NO-ELIP was determined using a previously developed syringe/vacuum method, 19 and confirmed by measuring the echogenicity of the liposomes using transvascular ultrasound imaging. NO-ELIP (380 µL) was added into 19 mL of phosphate-buffered saline (PBS) (Gibco™, Invitrogen Co, Carlsbad, CA, USA) to obtain a 50 × dilution factor.…”

Section: Preparation Of No-elipmentioning

confidence: 99%

“…[11][12][13] Successful delivery of NO to the cerebral arteries may help prevent the genesis of cerebral vasospasm and provide cerebral vascular relaxation in patients with subarachnoid hemorrhage. 14 Ultrasound contrast agents usually contain a perfluorcarbon gas stabilized by a shell of biocompatible material such as protein, 15 lipid, [16][17][18][19] or polymer. 20 We have recently developed a novel methodology to encapsulate bioactive gases replacing air into our liposomal nanovehicles.…”

Section: Introductionmentioning

confidence: 99%

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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DNA‐Coated Microbubbles with Biochemically Tunable Ultrasound Contrast Activity

et al. 2011

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Changing the mechanical properties of the microbubble shell in response to a biochemical stimulus leads to vast changes in both ultrasound-induced bubble dynamics and contrast-enhanced ultrasound imaging. Here, DNA-coated microbubbles are shown to be a simple and highly versatile platform that can silence and re-activate contrast activity in response to the introduction and removal of biochemical stimuli.

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Physical correlates of the ultrasonic reflectivity of lipid dispersions suitable as diagnostic contrast agents

Cited by 85 publications

References 33 publications

A Method to Co-Encapsulate Gas and Drugs in Liposomes for Ultrasound-Controlled Drug Delivery

A Method to Co-Encapsulate Gas and Drugs in Liposomes for Ultrasound-Controlled Drug Delivery

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

DNA‐Coated Microbubbles with Biochemically Tunable Ultrasound Contrast Activity

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