Ultrasonic Enhancement of Drug Penetration in Solid Tumors

Lai, Chun Yen; Fite, Brett Z.; Ferrara, Katherine W.

doi:10.3389/fonc.2013.00204

Cited by 37 publications

(24 citation statements)

References 120 publications

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“…Ultrasound is known to promote membrane permeability, thus increasing intracellular drug accumulation. Previous studies have suggested that the mechanisms by which ultrasound enhances the cytotoxicity of chemotherapy drugs include increased generation of reactive oxygen species [10,11], intracellular drug accumulation [12,13], and cell membrane permeability [14,15,16]. The combined therapy concentration and sufficient exposure time were crucial to the chemotherapeutic efficacy in our study.…”

Section: Discussionmentioning

confidence: 56%

Low-Frequency Ultrasound Enhances Paclitaxel Efficacy in EMT6 Subcutaneous Tumors in Balb/c Mice

Weng¹,

Chen

Zhao

et al. 2016

Oncol Res Treat

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Background: The objective of this study was to explore the effects of 30 kHz ultrasound on the efficacy of paclitaxel in subcutaneous breast tumors in Balb/c mice in vivo. Materials and Methods: 40 Balb/c female mice were divided into 5 groups: model control group, paclitaxel intraperitoneal (ip) group (20 mg/kg, ip, at 3 day intervals for a total of 3 doses (q3d×3)), paclitaxel intratumoral (it) group (20 mg/kg, it, q3d×3), paclitaxel intraperitoneal (20 mg/kg, ip, q3d×3) combined with low-frequency ultrasound (LFU) group, and paclitaxel intratumoral (20 mg/kg, it, q3d×3) combined with LFU group. Ultrasound parameters were 30 kHz, 200 MW intensity, 15 min, q3d×3. The antitumoral effect was determined by examining the tumor weight in subcutaneously inoculated EMT6 breast carcinoma models in Balb/c mice. All subcutaneous tumors were examined using high performance liquid chromatography (HPLC) upon completion of the experiments. Drug concentrations in the subcutaneous tumors were also analyzed using HPLC. Finally, paraffin sections of the subcutaneous tumors were made, and after hematoxylin and eosin staining, the tumor morphology was examined under a light microscope. Results: LFU combined with paclitaxel significantly restrained tumor growth in transplanted subcutaneous EMT6 tumors in Balb/c mice, and this effect correlated with increased local concentrations of paclitaxel in the tumors. Body weight measurement did not reveal significant adverse effects on the Balb/c mice during the study. Conclusion: LFU combined with paclitaxel has a significant synergistic effect in the treatment of breast cancer.

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Section: Discussionmentioning

confidence: 56%

Low-Frequency Ultrasound Enhances Paclitaxel Efficacy in EMT6 Subcutaneous Tumors in Balb/c Mice

Weng¹,

Chen

Zhao

et al. 2016

Oncol Res Treat

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“…Several good reviews on the use of HIFU in nanoparticle drug delivery have been published [27, 103–105]. Ultrasound technology can impart both thermal and mechanical effects to improve liposome drug delivery.…”

Section: Current Strategiesmentioning

confidence: 99%

“…The prolific tumor-responsive liposome literature is beyond the scope of this article but has been recently reviewed [21–23]. A different strategy highlighted in this article is the use of liposome formulations responsive to external stimuli (hyperthermia, radiofrequency ablation, ultrasound, magnetic field, and radiotherapy) [3, 21–27]. By applying an external stimulus to the local tumor region, the liposomes located within the tumor are triggered to release their drug payload.…”

Section: Introductionmentioning

confidence: 99%

Strategies for improving the intratumoral distribution of liposomal drugs in cancer therapy

Goins

Phillips

Bao

2016

Expert Opinion on Drug Delivery

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Introduction A major limitation of current liposomal cancer therapies is the inability of liposome therapeutics to penetrate throughout the entire tumor mass. This inhomogeneous distribution of liposome therapeutics within the tumor has been linked to treatment failure and drug resistance. Both liposome particle transport properties and tumor microenvironment characteristics contribute to this challenge in cancer therapy. This limitation is relevant to both intravenously and intratumorally administered liposome therapeutics. Areas covered Strategies to improve the intratumoral distribution of liposome therapeutics are described. Combination therapies of intravenous liposome therapeutics with pharmacologic agents modulating abnormal tumor vasculature, interstitial fluid pressure, extracellular matrix components, and tumor associated macrophages are discussed. Combination therapies using external stimuli (hyperthermia, radiofrequency ablation, magnetic field, radiation, and ultrasound) with intravenous liposome therapeutics are discussed. Intratumoral convection-enhanced delivery (CED) of liposomal therapeutics is reviewed. Expert opinion Optimization of the combination therapies and drug delivery protocols are necessary. Further research should be conducted in appropriate cancer types with consideration of physiochemical features of liposomes and their timing sequence. More investigation of the role of tumor associated macrophages in intratumoral distribution is warranted. Intratumoral infusion of liposomes using CED is a promising approach to improve their distribution within the tumor mass.

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“…Diffusion through skin may be enhanced by sonophoresis (phonophoresis), electrophoresis (iontophoresis), external pressure, and massage [20,[41][42][43][44][45][46]. The major advantage of these methods is considerable reduction of treatment time from hours down to several ten minutes [41,[47][48][49][50][51][52][53][54][55][56]. Skin optoporation based on fractional tissue ablation with pulsed lamp or Er:YAG laser radiation was reported to considerably enhance epidermal permeability for OC agents and nanoparticles [57][58][59].…”

Section: Introductionmentioning

confidence: 99%

Optical clearing in photoacoustic flow cytometry

Menyaev

Nedosekin

Sarimollaoglu

et al. 2013

Biomed. Opt. Express

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Clinical applications of photoacoustic (PA) flow cytometry (PAFC) for detection of circulating tumor cells in deep blood vessels are hindered by laser beam scattering, that result in loss of PAFC sensitivity and resolution. We demonstrate biocompatible and rapid optical clearing (OC) of skin to minimize light scattering and thus, increase optical resolution and sensitivity of PAFC. OC effect was achieved in 20 min by sequent skin cleaning, microdermabrasion, and glycerol application enhanced by massage and sonophoresis. Using ~0.8 mm mouse skin layer over a blood vessel in vitro phantom we demonstrated 1.6-fold decrease in laser spot blurring accompanied by 1.6-fold increase in PA signal amplitude from blood background. As a result, peak rate for B16F10 melanoma cells in blood flow increased 1.7-fold. By using OC we also demonstrated the feasibility of PA contrast improvement for human hand veins.

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Ultrasonic Enhancement of Drug Penetration in Solid Tumors

Cited by 37 publications

References 120 publications

Low-Frequency Ultrasound Enhances Paclitaxel Efficacy in EMT6 Subcutaneous Tumors in Balb/c Mice

Low-Frequency Ultrasound Enhances Paclitaxel Efficacy in EMT6 Subcutaneous Tumors in Balb/c Mice

Strategies for improving the intratumoral distribution of liposomal drugs in cancer therapy

Optical clearing in photoacoustic flow cytometry

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