Ultrasound-Mediated Drug/Gene Delivery in Solid Tumor Treatment

Division of Engineering Mechanics, School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore.
Journal of healthcare engineering 06/2013; 4(2):223-54. DOI: 10.1260/2040-2295.4.2.223
Source: PubMed

ABSTRACT Ultrasound is an emerging modality for drug delivery in chemotherapy. This paper reviews this novel technology by first introducing the designs and characteristics of three classes of drug/gene vehicles, microbubble (including nanoemulsion), liposomes, and micelles. In comparison to conventional free drug, the targeted drug-release and delivery through vessel wall and interstitial space to cancerous cells can be activated and enhanced under certain sonication conditions. In the acoustic field, there are several reactions of these drug vehicles, including hyperthermia, bubble cavitation, sonoporation, and sonodynamics, whose physical properties are illustrated for better understanding of this approach. In vitro and in vivo results are summarized, and future directions are discussed. Altogether, ultrasound-mediated drug/gene delivery under imaging guidance provides a promising option in cancer treatment with enhanced agent release and site specificity and reduced toxicity.

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    ABSTRACT: Aims: Liposomes are spherical vesicles composed of concentric phospholipid bilayers that can entrap hydrophilic, hydrophobic and amphiphilic drugs. Liposomes can be prepared from natural phospholipids, synthetic lipids or bacterial lipids. Regarding to the easy access to microorganisms in all year round, being economic and possibly growing in various substrates, bacterial lipids can be suitable candidates for preparation of liposomes. Objective: The aim of the present study was to formulate and evaluate liposomal vesicles prepared by lipid extracted from E. coli and loaded with methylene blue as drug model. Material and Methods: The lipids were extracted from the bacteria E.coli and analyzed by High Performance Thin-Layer Chromatography (HPTLC). Liposomes were prepared using film method and then characterized by Differential Scanning Calorimetry (DSC), and their particle sizes were measured. The release of methylene blue was determined using dialysis membrane method. Results: HPTLC analysis of the extracted lipids indicated that the glycerol ether was the major lipid with more than 70 percent probability. Results of particle size determinationshowed a mean size of 338 nm. The DSC curve of liposomes without methylene blue was different from methylene blue containing liposomes that indicated the possible interaction methylene blue with lipids during the preparation of liposomes. Encapsulation efficiency was 53.33±2.88% and there was 97.54%±0.00 release after 24 h. Conclusion: The results of this study may indicate the possible use bacterial lipids in preparation of nano-drug delivery derived system.
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    ABSTRACT: Techniques for controlling the rate and duration of drug delivery, whilst targeting specific locations of the body for treatment, to deliver the cargo (drugs or DNA) to particular parts of the body by what are becoming called "smart drug carriers" have gained increased attention during recent years. Using such smart carriers, researchers have also been investigating a number of physical energy forces including: magnetic fields, ultrasound, electric fields, temperature gradients, photoactivation or photorelease mechanisms, and mechanical forces to enhance drug delivery within the targeted cells or tissues and also to activate the drugs using a similar or a different type of external trigger. This review aims to cover a number of such physical energy modalities. Various advanced techniques such as magnetoporation, electroporation, iontophoresis, sonoporation/mechnoporation, phonophoresis, optoporation and thermoporation will be covered in the review. Special emphasis will be placed on photodynamic therapy owing to the experience of the authors' laboratory in this area, but other types of drug cargo and DNA vectors will also be covered. Photothermal therapy and theranostics will also be discussed.
    Advanced drug delivery reviews 06/2013; DOI:10.1016/j.addr.2013.05.010 · 11.96 Impact Factor
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    ABSTRACT: Abstract Purpose/aim of study: Drug delivery to the ocular posterior segment is of importance, but it is a challenge in the treatment of irreversible blindness disease, such as age-related macular degeneration. Although some methods (i.e. intraocular injection, sustained release by polymer and iontophoresis) have been applied, some technical drawbacks, such as slow rate and damage to the eye, need to be overcome for wide use. Materials and methods: In this study, the feasibility of high-intensity focused ultrasound (HIFU) to enhance the transsclera drug delivery was tested for the first time. One-hundred HIFU pulses with the driving frequency of 1.1 MHz, acoustic power of 105.6 W, pulse duration of 10-50 ms and pulse repetition frequency of 1 Hz were delivered to the fresh ex vivo porcine sclera specimen. Results: In comparison to the passive diffusion (control), 50-ms HIFU can increase the penetration depth by 2.0 folds (501.7 ± 126.4 µm versus 252.4 ± 29.2 µm) using bicinchoninic acid assay and Rhodamine 6 G fluorescence intensity by 3.1 folds (22.4 ± 12.3 versus 7.1 ± 4.1) and coverage area by 2.6 folds (40.4 ± 9.1% versus 15.8 ± 2.9%). No morphological changes on the sonicated sclera samples were found using a surface electron microscope. Conclusions: In summary, pulsed-HIFU may be an effective modality in the transsclera drug delivery with a high transporting rate and depth. In vivo studies are necessary to further evaluate its performance, including the drug penetration and its possible side effects.
    Current Eye Research 11/2014; DOI:10.3109/02713683.2014.980006 · 1.66 Impact Factor


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Feb 3, 2015