Determination of threshold energy dose for ultrasound-induced transdermal drug transport

Mitragotri, Samir; Farrell, J. M.; Tang, Hua; Terahara, Takaaki; Kost, Joseph; Langer, Robert

doi:10.1016/s0168-3659(99)00178-9

Cited by 136 publications

(76 citation statements)

References 15 publications

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“…There are numerous publications reporting ultrasonic intensity thresholds for an observed biological effect [15,[27][28][29][30][31][32][33][34][35][36]. These thresholds are usually different than thresholds for collapse cavitation and vary based on the type of cells or tissue and the mechanism producing the effect (permeabilizing cells, DNA delivery, lysis or tissue damage).…”

Section: Discussionmentioning

confidence: 99%

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The role of cavitation in acoustically activated drug delivery

Husseini

Rosa

Richardson

et al. 2005

Journal of Controlled Release

156

139

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Pluronic P105 micelles are potential candidates as chemotherapy drug delivery vehicles using ultrasonic stimulation as a release trigger. Acoustic power has been previously shown to release two anthracycline agents from these polymeric carriers. In this study, an ultrasonic exposure chamber with fluorescence detection was used to examine the mechanism of doxorubicin release from P105 micelles. Acoustic spectra were collected and analyzed, at the same spatial position as fluorescence data, to probe the role of cavitation in drug release. Our study showed a strong correlation between percent drug release and subharmonic acoustic emissions, and we attribute the drug release to collapse cavitation that perturbs the structure of the micelle and releases drug.

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Section: Discussionmentioning

confidence: 99%

“…The group of Mitrogotri has convincingly shown that the thresholds for producing skin permeability are a strong function of ultrasonic frequency [13,31,35,37,38]. As an example, the threshold for permeabilizing skin with 76.6 kHz is approximately 0.9 W/cm 2 [35].…”

Section: Discussionmentioning

confidence: 99%

The role of cavitation in acoustically activated drug delivery

Husseini

Rosa

Richardson

et al. 2005

Journal of Controlled Release

156

139

View full text Add to dashboard Cite

show abstract

“…methods such as iontophoresis that enhance penetration of drug molecules through the skin are applied (Mitragotri et al, 2000;Tao & Desai, 2003). Furthermore, vesicular carriers, microemulsions, lipidic and polymeric particulate carrier systems ensure dermal administration of drugs by dermal targeting and enterance of drugs into systemic circulation (Neubert, 2011;Benson, 2005).…”

Section: Overcoming the Barrier Properties Of The Skinmentioning

confidence: 99%

Novel Formulation Approaches for Dermal and Transdermal Delivery of Non-Steroidal Anti-Inflammatory Drugs

Okyar¹,

Özsoy²,

Güngör³

2012

Rheumatoid Arthritis - Treatment

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“…Ultrasound can open tiny holes in the cell membrane, making the cells temporarily permeable in localized areas and improving drug penetration. 15 This phenomenon improves drug effectiveness, reduces dosage requirements and toxicity, and enables clinicians to deliver drugs to specific areas of the body for localized treatment. Ultrasound opened a new approach to implementing gene transfection.…”

mentioning

confidence: 99%

Bioeffects of Low-Frequency Ultrasonic Gene Delivery and Safety on Cell Membrane Permeability Control

Wang

Bian

Wu³

et al. 2004

Journal of Ultrasound in Medicine

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Objective. To develop a novel method of ultrasonic naked gene delivery (UNGD); to examine the relationship between optimal parameters of ultrasound exposure and cell membrane permeability, enzymes, and free radicals; and to find optimal control parameters that were realizable, reliable, and noncytotoxic for use in gene therapy. Methods. Suspensions of chicken, rabbit, and rat red blood cells and S180 cells were exposed to a calibrated ultrasonic field with different parameters in both the still and flowing states to obtain optimal parameters for UNGD. The optimal parameters then were used to implement UNGD. We examined morphologic characteristics, membrane permeability, enzymes, free radicals, naked gene expression efficiency, cell damage threshold, and cell viability by laser scanning confocal microscopy, fluorescent microscopy, flow cytometry, and spectrophotometry. Results. Green fluorescent protein (GFP) as a reporter was delivered into S180 cells under the optimal parameters without cell damage or cytotoxicity. The transfection rate (mean ± SD) was approximately 35.83% ± 2.53% (n = 6) in viable cells, and cell viability was 90.17% ± 1.47% (n = 6). The intensity of GFP expression with UNGD showed a higher fluorescent peak over both an adeno-associated virus vector-GFP group and a control group (P < .001). Additionally, malondialdehyde, hydroxyl free radicals, alkaline phosphatase, and acid phosphatase displayed an S-shaped growth model (r = 0.98 ± 0.01) in response to permeability and morphologic alteration. Conclusions. Under optimal conditions, low-frequency ultrasound can safely deliver naked genes into cells without causing cell damage. The analytical results indicate that, except for subcavitation, free radical products are responsible for bioeffects in gene delivery. The constant E of energy deposition at 90% cell viability is the optimal control factor, and 80% viability represents the damage threshold. Optimal gene uptake by cells and safety depend on E. Constant E can be applied to control the gene delivery effect in combination with other parameters.

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Determination of threshold energy dose for ultrasound-induced transdermal drug transport

Cited by 136 publications

References 15 publications

The role of cavitation in acoustically activated drug delivery

The role of cavitation in acoustically activated drug delivery

Novel Formulation Approaches for Dermal and Transdermal Delivery of Non-Steroidal Anti-Inflammatory Drugs

Bioeffects of Low-Frequency Ultrasonic Gene Delivery and Safety on Cell Membrane Permeability Control

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