Echogenic lipsomes for targeted drug delivery

Holland, Christy K.; McPherson, David D.

doi:10.1109/isbi.2009.5193159

Cited by 14 publications

(14 citation statements)

References 23 publications

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“…[63][64][65][66] ELIPs have also been investigated as a cavitation nucleation agent in addition to their role as a diagnostic ultrasound contrast agents. 67,68 Although nonlinear bubble oscillations were not examined in this study, the results indicate that ELIPs may be able to nucleate cavitation across a broad range of frequencies due to their broad size distribution. Thus drug-loaded ELIPs may be effective in various therapeutic applications, including ultrasound-enhanced thrombolysis and ultrasound-mediated drug delivery.…”

Section: Discussionmentioning

confidence: 90%

Acoustic characterization of echogenic liposomes: Frequency-dependent attenuation and backscatter

Kopechek

Haworth

Raymond

et al. 2011

The Journal of the Acoustical Society of America

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Ultrasound contrast agents (UCAs) are used clinically to aid detection and diagnosis of abnormal blood flow or perfusion. Characterization of UCAs can aid in the optimization of ultrasound parameters for enhanced image contrast. In this study echogenic liposomes (ELIPs) were characterized acoustically by measuring the frequency-dependent attenuation and backscatter coefficients at frequencies between 3 and 30 MHz using a broadband pulse-echo technique. The experimental methods were initially validated by comparing the attenuation and backscatter coefficients measured from 50-μm and 100-μm polystyrene microspheres with theoretical values. The size distribution of the ELIPs was measured and found to be polydisperse, ranging in size from 40 nm to 6 μm in diameter, with the highest number observed at 65 nm. The ELIP attenuation coefficients ranged from 3.7 ± 1.0 to 8.0 ± 3.3 dB/cm between 3 and 25 MHz. The backscatter coefficients were 0.011 ± 0.006 (cm str)(-1) between 6 and 9 MHz and 0.023 ± 0.006 (cm str)(-1) between 13 and 30 MHz. The measured scattering-to-attenuation ratio ranged from 8% to 22% between 6 and 25 MHz. Thus ELIPs can provide enhanced contrast over a broad range of frequencies and the scattering properties are suitable for various ultrasound imaging applications including diagnostic and intravascular ultrasound.

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Section: Discussionmentioning

confidence: 90%

Acoustic characterization of echogenic liposomes: Frequency-dependent attenuation and backscatter

Kopechek

Haworth

Raymond

et al. 2011

The Journal of the Acoustical Society of America

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“…Ultrasound helps to overcome various biological barriers the drug encounters on the way to its target. First, the ultrasound radiation force pushes nanoparticles through blood capillary walls thus enhancing extravasation of nanoparticle drug carries or macromolecular drugs [12, 66–69]. Second, even a moderate temperature increase may significantly increase the permeability of blood capillaries [70, 71].…”

Section: Discussionmentioning

confidence: 99%

Ultrasound-mediated tumor imaging and nanotherapy using drug loaded, block copolymer stabilized perfluorocarbon nanoemulsions

Rapoport

Nam

Gupta

et al. 2011

Journal of Controlled Release

372

399

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Perfluorocarbon nanoemulsions can deliver lipophilic therapeutic agents to solid tumors and simultaneously provide for monitoring nanocarrier biodistribution via ultrasonography and/or 19F MRI. In the first generation of block copolymer stabilized perfluorocarbon nanoemulsions, perfluoropentane (PFP) was used as the droplet forming compound. Although manifesting excellent therapeutic and ultrasound imaging properties, PFP nanoemulsions were unstable at storage, difficult to handle, and underwent hard to control phenomenon of irreversible droplet-to-bubble transition upon injection. To solve the above problems, perfluoro-15-crown-5-ether (PFCE) was used as a core forming compound in the second generation of block copolymer stabilized perfluorocarbon nanoemulsions. PFCE nanodroplets manifest both ultrasound and fluorine (19F) MR contrast properties, which allows using multimodal imaging and 19F MR spectroscopy for monitoring nanodroplet pharmacokinetics and biodistribution. In the present paper, acoustic, imaging, and therapeutic properties of unloaded and paclitaxel (PTX) loaded PFCE nanoemulsions are reported. As manifested by the 19F MR spectroscopy, PFCE nanodroplets are long circulating, with about 50% of the injected dose remaining in circulation two hours after the systemic injection. Sonication with 1-MHz therapeutic ultrasound triggered reversible droplet-to-bubble transition in PFCE nanoemulsions. Microbubbles formed by acoustic vaporization of nanodroplets underwent stable cavitation. The nanodroplet size (200 nm to 350 nm depending on a type of the shell and conditions of emulsification) as well as long residence in circulation favored their passive accumulation in tumor tissue that was confirmed by ultrasonography. In the breast and pancreatic cancer animal models, ultrasound-mediated therapy with paclitaxel-loaded PFCE nanoemulsions showed excellent therapeutic properties characterized by tumor regression and suppression of metastasis. Anticipated mechanisms of the observed effects are discussed.

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“…The mismatch between acoustic impedances of water or tissue (1.4 MRayl) and PFC (approximately 0.3 MRayl) may promote generation of sheer stresses in the presence of microbubbles. Acoustic streaming and radiation force can also push nanoparticles through blood capillary walls thus enhancing extravasation of drug carriers or macromolecular drugs [59,60,62,138,139]. In an interesting new application, the ultrasound radiation force was used to modulate ligand exposure on the surface of targeted contrast agents [140].…”

Section: Targeted Drug-delivery Mechanismsmentioning

confidence: 99%

Phase-shift, stimuli-responsive Drug Carriers for Targeted Delivery

O’Neill

Rapoport

2011

Therapeutic Delivery

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The intersection of particles and directed energy is a rich source of novel and useful technology that is only recently being realized for medicine. One of the most promising applications is directed drug delivery. This review focuses on phase-shift nanoparticles (that is, particles of submicron size) as well as micron-scale particles whose action depends on an external-energy triggered, first-order phase shift from a liquid to gas state of either the particle itself or of the surrounding medium. These particles have tremendous potential for actively disrupting their environment for altering transport properties and unloading drugs. This review covers in detail ultrasound and laser-activated phase-shift nano- and micro-particles and their use in drug delivery. Phase-shift based drug-delivery mechanisms and competing technologies are discussed.

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Echogenic lipsomes for targeted drug delivery

Cited by 14 publications

References 23 publications

Acoustic characterization of echogenic liposomes: Frequency-dependent attenuation and backscatter

Acoustic characterization of echogenic liposomes: Frequency-dependent attenuation and backscatter

Ultrasound-mediated tumor imaging and nanotherapy using drug loaded, block copolymer stabilized perfluorocarbon nanoemulsions

Phase-shift, stimuli-responsive Drug Carriers for Targeted Delivery

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