Ultrasound-facilitated thrombolysis using tissue-plasminogen activator-loaded echogenic liposomes

Tiukinhoy-Laing, Susan D.; Huang, Shaoling; Klegerman, Melvin E.; Holland, Christy K.; McPherson, David D.

doi:10.1016/j.thromres.2006.06.009

Cited by 120 publications

(94 citation statements)

References 41 publications

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“…Lipids and polymers can be engineered to self-assemble into vehicles that protect or concentrate drugs, particularly those with systemic toxicity [19][20][21][22]. The mechanical or thermal properties of ultrasound can release the drug from the vehicle in the selected region of interest.…”

Section: Mechanical or Thermal Changes In Delivery Vehiclesmentioning

confidence: 99%

“…Activatable liposomes can release a drug by the mechanical effects of ultrasound, enhanced by the inclusion of small air pockets within the membrane [19,20] or by heating beyond the phase transition temperature of the lipids within the membrane [21]. Advantages of liposomes as carriers include, the fusigenic nature of the membrane, and a reasonably high drug loading efficiency (up to 0.25 mg drug/mg lipid).…”

Section: Vehiclesmentioning

confidence: 99%

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Driving delivery vehicles with ultrasound

Ferrara

2008

Advanced Drug Delivery Reviews

225

162

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Therapeutic applications of ultrasound have been considered for over 40 years, with the mild hyperthermia and associated increases in perfusion produced by ultrasound harnessed in many of the earliest treatments. More recently, new mechanisms for ultrasound-based or ultrasound-enhanced therapies have been described, and there is now great momentum and enthusiasm for the clinical translation of these techniques. This dedicated issue of Advanced Drug Delivery Reviews, entitled "Ultrasound for Drug and Gene Delivery," addresses the mechanisms by which ultrasound can enhance local drug and gene delivery and the applications that have been demonstrated at this time. In this commentary, the identified mechanisms, delivery vehicles, applications and current bottlenecks for translation of these techniques are summarized. KeywordsUltrasound; Therapy; Drug delivery; Gene delivery; Sonoporation; Cavitation As an imaging modality, ultrasound is widely employed and valued for its real time applications, low cost, simplicity, and safety. Waves of alternating increased and decreased pressure propagate from the transducer, typically resulting in a maximum intensity in a focal region chosen by the operator. The dimensions of the focal region can vary from tens of microns for high frequency ultrasound to centimeters for an unfocused therapeutic beam. Most clinical instruments are engineered to effectively image from the body surface to 24 or more centimeters in depth. The ability to locally control and maximize energy deposition deep within the body facilitates a broad range of clinical opportunities for ultrasound imaging and therapy. Developing over four decades, clinical and commercial application of ultrasonic therapies spans hyperthermia, drug delivery, lipoplasty, and thrombolysis [1,2]. A complete and precise summary of the potential applications for ultrasonic enhancement of drug and gene delivery remains challenging as the mechanisms are multiple and not fully characterized. From an engineering viewpoint, the methods by which ultrasound facilitates drug and gene delivery can be summarized as direct changes in the biological or physiological properties of tissues facilitating transport, direct changes in the drug or vehicle increasing bioavailability or enhancing efficacy, and indirect effects by which ultrasound acts on the vehicle to produce changes in the surrounding tissue. While there are common mechanisms between these methods, the engineering challenges associated with the optimization of ultrasound systems and drug and vehicle design are unique for each method. Promising examples of each of these methods can be identified at this time and are addressed below.☆ This commentary is part of the Advanced Drug Delivery Reviews theme issue on "Ultrasound in Drug and Gene Delivery".

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Section: Mechanical or Thermal Changes In Delivery Vehiclesmentioning

confidence: 99%

Section: Vehiclesmentioning

confidence: 99%

Driving delivery vehicles with ultrasound

Ferrara

2008

Advanced Drug Delivery Reviews

225

162

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“…8) [70]. The effective delivery of the adhered drug is relevant to the echogenicity or the ability to bounce a signal base on oscillation, growth, and collapse of the microbubble system [71]. The echogenicity is affected by the choice of component mixtures such as water and PFP, the surfactant, and the size of the microbubble system.…”

Section: Ultrasound-sensitive Drug Deliverymentioning

confidence: 99%

Smart Drug Delivery Strategies Based on Porous Nanostructure Materials

Wang¹,

Huang²,

Lai³

2016

Smart Drug Delivery System

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The control of drug delivery can have a great effect on its efficacy. An optimum concentration range of drugs can play a significant role in the human body, and it can cause harm to humans when it exceeds the range of the drug concentration. Recently, a variety of drug deliveries and their targeted systems have been studied to minimize drug loss and maximize the amount of drug accumulated in the required area, thus increasing drug bioavailability. In addition, we should especially consider the prevention of its harmful side-effects in the human body. Innovative drug delivery systems based on biodegradable, natural or synthetic polymers, micro-or nano-particles, lipoproteins, micelles, TiO 2 nanotube arrays (TNTs), nanoporous anodic aluminum oxide (AAO), and so on were developed, which combined magnetic targeting and stimulus-responsive in drug delivery systems. The composition of delivery carriers and the stimulus-responsive elements proved stimulus-responsive drug release as a smart drug delivery system.

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“…Following a 50% t-Pa entrapment into eliP, ex vivo porcine clots treated with tPa-loaded echogenic liposomes were lysed with an effect similar to treatment with free t-Pa. 36 t-Pa can also be delivered as a PeGylated anionic gelatin complex 37 or in microbubbles with the arg-Gly-asp-ser (rGds) tetrapeptide as a targeting agent. 38 in both cases, after iv injection in a rabbit model, t-Pa was released from the nano-sized delivery complex when exposed to ultrasound.…”

Section: Thrombolytic Therapy With Polymeric Nanocarriers and Immunolmentioning

confidence: 99%