Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, noncavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin's barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase its impact on medicine.

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Transdermal drug delivery

Laser-induced breakdown spectroscopy (LIBS) has become a very popular analytical method in the last decade in view of some of its unique features such as applicability to any type of sample, practically no sample preparation, remote sensing capability, and speed of analysis The technique has a remarkably wide applicability in many fields, and the number of applications is still growing From an analytical point of view, the quantitative aspects of LIBS may be considered its Achilles' heel, first due to the complex nature of the laser–sample interaction processes, which depend upon both the laser characteristics and the sample material properties, and second due to the plasma–particle interaction processes, which are space and time dependent Together, these may cause undesirable matrix effects Ways of alleviating these problems rely upon the description of the plasma excitation-ionization processes through the use of classical equilibrium relations and therefore on the assumption that the laser-induced 

Laser-Induced Breakdown Spectroscopy (LIBS), Part I: Review of Basic Diagnostics and Plasma–Particle Interactions: Still-Challenging Issues Within the Analytical Plasma Community

Triggerable drug delivery systems enable on-demand controlled release profiles that may enhance therapeutic effectiveness and reduce systemic toxicity. Recently, a number of new materials have been developed that exhibit sensitivity to visible light, near-infrared (NIR) light, ultrasound, or magnetic fields. This responsiveness can be triggered remotely to provide flexible control of dose magnitude and timing. Here we review triggerable materials that range in scale from nano to macro, and are activated by a range of stimuli.

Remotely triggerable drug delivery systems.

Harnessing the ability to precisely and reproducibly actuate fluids and manipulate bioparticles such as DNA, cells, and molecules at the microscale, microfluidics is a powerful tool that is currently revolutionizing chemical and biological analysis by replicating laboratory bench-top technology on a miniature chip-scale device, thus allowing assays to be carried out at a fraction of the time and cost while affording portability and field-use capability. Emerging from a decade of research and development in microfluidic technology are a wide range of promising laboratory and consumer biotechnological applications from microscale genetic and proteomic analysis kits, cell culture and manipulation platforms, biosensors, and pathogen detection systems to point-of-care diagnostic devices, high-throughput combinatorial drug screening platforms, schemes for targeted drug delivery and advanced therapeutics, and novel biomaterials synthesis for tissue engineering. The developments associated with these technological advances along with their respective applications to date are reviewed from a broad perspective and possible future directions that could arise from the current state of the art are discussed.

Microfluidic Devices for Bioapplications

Approaches for breaking the barriers of drug permeation through transdermal drug delivery.

Low-frequency sonophoresis: current status and future prospects.

Background and Objectives

Much interest has been shown in the use of lasers for nonviral targeted gene transfer, since the spatial characteristics of laser light are quite well defined. The aim of this study was to demonstrate in vivo gene transfer by the use of laser-induced stress waves (LISWs).



Study Design/Materials and Methods

After reporter genes had been intradermally injected to rat skin in vivo, a laser target was placed on the gene-injected skin. LISWs were generated by the irradiation of an elastic laser target with 532-nm nanosecond laser pulses of a Q-switched Nd:YAG laser.



Results

Levels of luciferase activities for the skin exposed to LISWs were two orders of magnitude higher than those for the skin injected with naked DNA. Expressions of enhanced green fluorescent protein (EGFP) and β-galactosidase were observed only in the area that was exposed to LISWs, and in addition, epidermal cells were selectively transfected. No major side effects were observed, and luciferase activity levels as high as 105 RLU per mg of protein were sustained even 5 days after gene transfer.



Conclusion

Highly efficient and site-specific gene transfer can be achieved by applying a few pulses of nanosecond pulsed LISWs to rat skin in vivo. Lasers Surg. Med. 34:242–248, 2004. © 2004 Wiley-Liss, Inc.

In vivo targeted gene transfer in skin by the use of laser-induced stress waves.

Plasmid DNA has been successfully delivered to mammalian cells by applying a nanosecond pulsed laser-induced stress wave (LISW). Cells exposed to a LISW were selectively transfected with plasmids coding for green fluorescent protein. It was also shown that transient, mild cellular heating (∼43 °C) was effective in improving the transfection efficiency.

Gene transfer into mammalian cells by use of a nanosecond pulsed laser-induced stress wave.

The current invention provides devices, methods and systems involving application of energy and/ or a liquefaction promoting medium to a tissue of interest to generate a liquefied sample comprising tissue constituents so as to provide for rapid tissue sampling, tissue decontamination as well as qualitative and/or quantitative detection of analytes that may be part of tissue constituents (e.g., several types of biomolecules, drugs, and microbes). In addition, the current invention provides specific compositions of the said liquefaction promoting medium so as to facilitate liquefaction, preserve liquefied tissue constituents, and enable delivery of molecules into tissues. Determination of tissue composition in the liquefied tissue sample can be used in a variety of applications, including diagnosis or prognosis of local as well as systemic diseases, evaluating bioavailability of therapeutics in different tissues following drug administration, forensic detection of drugs-of-abuse, evaluating changes in the tissue microenvironment following exposure to a harmful agent, and various other applications. The methods, devices and systems are used to deliver one or more drugs through or into the site of the tissue to be liquefied.

System, method and device for tissue-based diagnosis

Background and Objective

A large number of clinical trials of transmyocardial laser revascularization (TMLR) have been conducted to treat severe ischemic heart diseases. A variety of laser sources have been used or tested for this treatment, however, no comprehensive study has been performed to reveal the mechanism and the optimum laser irradiation condition for the myocardium tissue ablation. There have been reported limited experimental data of the high-intensity pulsed laser ablation of myocardium tissues.



Study Design/Materials and Methods

A 1064-nm Q-switched Nd:YAG laser and its 2nd (532 nm), 3rd (355 nm), and 4th (266 nm) harmonics were used for ablation experiments. At each wavelength, 25 laser pulses irradiated the porcine myocardium tissue samples at a constant laser intensity (peak laser power divided by laser spot area) of ∼2 GW/cm2 and the ablation depths were measured. During ablation, laser-induced optical and acoustic emissions were measured to investigate the ablation mechanism at each laser wavelength. For the ablated tissues, histological observation was made with a polarization optical microscope.



Results

It was shown that the ablation efficiency did not directly depend on the linear absorption coefficient of the tissue; the ablation depth was maximized at 355 and 1064 nm, and minimized at 532 nm. Strong laser-induced optical and acoustic emissions were observed for the 266- and 1064-nm laser irradiations. The histology showed that thermal denaturation of the tissue near the ablation walls decreased with decreasing wavelength for 266, 355, and 532 nm, but it was limited for 1064 nm.



Conclusion

At the laser intensity of ∼2 GW/cm2, ablation characteristics were drastically changed for the different laser wavelengths. The results indicated that for 266, 355, and 532 nm, the tissue removal was achieved mainly through a photothermal process, but for 266 nm the intense laser-induced plasma formation would result in a reduced laser energy coupling to the tissue. For 1064 nm, a photodisruption was most probable as a dominant tissue removal process. Because of the high ablation rate and limited thermal denaturation, the 355- and 1064-nm lasers could be potential laser sources for TMLR, although further investigation is needed to discuss the clinical issues. Lasers Surg. Med. 29:464–473, 2001. © 2001 Wiley-Liss, Inc.

Makoto Ogura

Papers

Low-frequency sonophoresis: current status and future prospects.

In vivo targeted gene transfer in skin by the use of laser-induced stress waves.

Gene transfer into mammalian cells by use of a nanosecond pulsed laser-induced stress wave.

System, method and device for tissue-based diagnosis

Nanosecond, high-intensity pulsed laser ablation of myocardium tissue at the ultraviolet, visible, and near-infrared wavelengths: in-vitro study.