Investigating the mechanism of acoustically activated uptake of drugs from Pluronic micelles

Husseini, Ghaleb A.; Runyan, Christopher M.; Pitt, William G.

doi:10.1186/1471-2407-2-20

Cited by 46 publications

(52 citation statements)

References 10 publications

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“…The polymer also appears to have a synergistic effect with some chemotherapeutic agents and has been proposed to inhibit the p-glycoprotein that causes multidrug resistance in many cancer cells (114). Pitt et al explored ultrasound as a means to induce drug release of doxorubicin from pluronic micelles (115,119). Even without ultrasound, pluronic has a synergistic effect with the doxorubicin, increasing the toxicity of the chemotherapeutic agent twofold in spite of decreased uptake of the doxorubicin into the cells.…”

Section: Site-specific Drug Releasementioning

confidence: 98%

“…Ultrasound treatment further increased the toxicity of the drug containing micelles another sixfold (118). In order to explain this, it was proposed that the presence of pluronic unimers aided the toxicity of the drug (119) but the micelles actually sequestered drug away from the cells until ultrasound induced drug release (115,119). The presence of sequestered drug inside the hydrophobic core was determined fluorescently using a doxorubicin analogue, ruboxyl, and it was found that up to 70% of the ruboxyl was sequestered inside of the micelles (118).…”

Section: Site-specific Drug Releasementioning

confidence: 99%

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Functionalized Micellar Systems for Cancer Targeted Drug Delivery

et al. 2007

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Polymer micelles are rapidly becoming a powerful nanomedicine platform for cancer therapeutic applications due to their small size (10-100 nm), in vivo stability, ability to solubilize water insoluble anticancer drugs, and prolonged blood circulation times. Recent data from clinical trials with three micelle formulations have highlighted these and other pharmacokinetic advantages with reduced systemic toxicity and patient morbidity compared to conventional drug formulation. While the initial anti-tumor efficacy of these systems seems promising, a strong research impetus has been placed on micelle functionalization in order to achieve tumor targeting and site-specific drug release, with the hope of reaching a more pronounced tumor response. Hence, the purpose of this review is to draw attention to the new developments of multi-functional polymer micelles for cancer therapy with special focus on tumor targeting and controlled drug release strategies.

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Section: Site-specific Drug Releasementioning

confidence: 98%

Section: Site-specific Drug Releasementioning

confidence: 99%

Functionalized Micellar Systems for Cancer Targeted Drug Delivery

et al. 2007

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“…Using fluorescent microscopy and flow cytometry, thy also reported that insonation enhanced the intracellular uptake of Pluronic micelles and its internalization into the nucleus of HL60 cells [178][179][180][181][182][183].…”

Section: Micellesmentioning

confidence: 99%

Ultrasonic drug delivery – a general review

Pitt

Husseini

Staples

2004

Expert Opinion on Drug Delivery

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557

428

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Ultrasound (US) has an ever-increasing role in the delivery of therapeutic agents including genetic material, proteins, and chemotherapeutic agents. Cavitating gas bodies such as microbubbles are the mediators through which the energy of relatively non-interactive pressure waves is concentrated to produce forces that permeabilize cell membranes and disrupt the vesicles that carry drugs. Thus the presence of microbubbles enormously enhances delivery of genetic material, proteins and smaller chemical agents. Delivery of genetic material is greatly enhanced by ultrasound in the presence of microbubbles. Attaching the DNA directly to the microbubbles or to gas-containing liposomes enhances gene uptake even further. US-enhanced gene delivery has been studied in various tissues including cardiac, vascular, skeletal muscle, tumor and even fetal tissue. US-enhanced delivery of proteins has found most application in transdermal delivery of insulin. Cavitation events reversibly disrupt the structure of the stratus corneum to allow transport of these large molecules. Other hormones and small proteins could also be delivered transdermally. Small chemotherapeutic molecules are delivered in research settings from micelles and liposomes exposed to ultrasound. Cavitation appears to play two roles: it disrupts the structure of the carrier vesicle and releases the drug; it also makes the cell membranes and capillaries more permeable to drugs. There remains a need to better understand the physics of cavitation of microbubbles and the impact that such cavitation has upon cells and drug-carrying vesicles.

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“…Despite the strong dose-dependent antiproliferative effect of antineoplastic drugs on cultured smooth muscle cells, their dosage is restricted in clinical cases because of their side effects. Recently, there have been several reports regarding the enhancement of drug uptake to the tissue by sonoporation [21][22][23][24][25][26]. Ultrasound induces to perturb the cell membrane and/or cell wall to render it more permeable to the drug, and enhances endocytosis or other activated uptake of the entire micelle (with the encapsulated drug) [21].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, there have been several reports regarding the enhancement of drug uptake to the tissue by sonoporation [21][22][23][24][25][26]. Ultrasound induces to perturb the cell membrane and/or cell wall to render it more permeable to the drug, and enhances endocytosis or other activated uptake of the entire micelle (with the encapsulated drug) [21]. Doxorubicin is one of the drugs whose uptake is enhanced by sonoporation [21,22].…”

Section: Introductionmentioning

confidence: 99%