Intracellular Uptake and Trafficking of Pluronic Micelles in Drug‐Sensitive and MDR Cells: Effect on the Intracellular Drug Localization

Rapoport, Natalya; Marin, Alexander; Luo, Yi; Prestwich, Glenn D.; Muniruzzaman, Md.

doi:10.1002/jps.10006

Cited by 119 publications

(64 citation statements)

References 25 publications

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“…It has also been shown that Pluronic copolymers can be absorbed into the cells, probably through an endocytic pathway (for Pluronics P-85, PL-35 PL-121, and PP-105, Batrakova et al, 2003;Rapoport et al, 2002). However, concerning PF-68, prior to the current study, it was still unknown if PF-68 polymer enters the cell.…”

Section: Introductionmentioning

confidence: 74%

“…Similarly, the broad use of other types of Pluronics for drug delivery (Pluronics P-85, L-61, F-127; or P-105, Batrakova et al, 1996;Kabanov et al, 2002;Rapoport et al, 2002) and gene delivery (Pluronics P-85, PL-61 and PF-127, Lemieux et al, 2000;Yang et al, 2005) also strongly suggests Pluronic trafficking through the cell membrane. It has also been shown that Pluronic copolymers can be absorbed into the cells, probably through an endocytic pathway (for Pluronics P-85, PL-35 PL-121, and PP-105, Batrakova et al, 2003;Rapoport et al, 2002).…”

Section: Introductionmentioning

confidence: 93%

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The fate of Pluronic F‐68 in chondrocytes and CHO cells

Gigout

Buschmann

Jolicœur

2008

Biotech & Bioengineering

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The surfactant Pluronic F-68 (PF-68) is widely used in large-scale mammalian cell culture to protect cells from shear stress that arises from agitation and gas sparging. Several studies suggested that PF-68 is incorporated into the cell plasma membrane and could enter the cells, but without providing any direct evidence. The current study has examined this question for two cell types, one of pharmaceutical interest (CHO cells) and the other of biomedical interest (chondrocytes or cartilage cells). A fluorescent derivative of PF-68 was synthesized to detect and localize internalized Pluronic with culture time. PF-68 uptake by the cells was quantified and characterized. We clearly demonstrate that PF-68 enters the cells, and possibly accumulates in the endocytic pathway. CHO cells showed an average uptake of 11.7 +/- 6.7 (SEM) microg PF-68/10(6) cells while the uptake of chondrocytes was 56.0 +/- 10.9 (SEM) microg PF-68/10(6) cells, independently of the initial PF-68 concentration (between 0.01 and 0.2%, w/v) and of cell concentration (from 1 x 10(6) to 4 x 10(6) cells/mL). These uptake values were identical for both static and agitated culture conditions. Finally, we found that CHO cells are able to eliminate intracellular fluorescent PF-68 but chondrocytes are not. These results show that the uptake of PF-68 by the cells can severely affect PF-68 concentration in the culture medium and thus shear protection effect.

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Section: Introductionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 93%

The fate of Pluronic F‐68 in chondrocytes and CHO cells

Gigout

Buschmann

Jolicœur

2008

Biotech & Bioengineering

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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

546

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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“…These experiments have quantified Dox uptake kinetics and isotherms in several studies (56,77,78). Ultrasound and the presence of Pluronic ® has a large influence on the uptake of Dox by drug sensitive and drug resistant breast cancer cells (A2780 and A2780/ ADR) (80). Insonation increased uptake in both cell lines; Pluronic ® at 10% reduced the amount of uptake compared to 0.1% Pluronic ® (81).…”

Section: In Vitro Research and Mechanism Of Ultrasound-cell Interactionmentioning

confidence: 99%

The Use of Ultrasound and Micelles in Cancer Treatment

Husseini

Pitt²

2008

j nanosci nanotechnol

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The high toxicity of potent chemotherapeutic drugs like Doxorubicin (Dox) limits the therapeutic window in which they can be applied. This window can be expanded by controlling the drug delivery in both space and time such that non-targeted tissues are not adversely affected. Recent research has shown that ultrasound (US) can be used to control the release of Dox and other hydrophobic drugs from polymeric micelles in both time and space. It has also been shown using an in vivo rat tumor model that Dox activity can be enhanced by ultrasound in one region, while in an adjacent region there is little or no effect of the drug. In this article, we review the in vivo and in vitro research being conducted in the area of micellar drug delivery and ultrasound to cancerous tissues. Additionally, we summarize our previously published mathematical models that attempt to represent the release and re-encapsulation phenomena of Dox from Pluronic ® P105 micelles upon the application of ultrasound. The potential benefits of such controlled chemotherapy compels a thorough investigation of role of ultrasound (US) and the mechanisms by which US accomplishes drug release and/or enhances drug potency. Therefore we will summarize our findings related the mechanism involved in acoustically activated micellar drug delivery to tumors.

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Intracellular Uptake and Trafficking of Pluronic Micelles in Drug‐Sensitive and MDR Cells: Effect on the Intracellular Drug Localization

Cited by 119 publications

References 25 publications

The fate of Pluronic F‐68 in chondrocytes and CHO cells

The fate of Pluronic F‐68 in chondrocytes and CHO cells

Ultrasonic drug delivery – a general review

The Use of Ultrasound and Micelles in Cancer Treatment

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