Cavitation-enhanced delivery of insulin in agar and porcine models of human skin.

Ultrasound-assisted transdermal insulin delivery offers a less painful and less invasive alternative to subcutaneous insulin injections. However, ultrasound-based drug delivery, otherwise known as sonophoresis, is a highly variable phenomenon, in part dependent on cavitation. The aim of the current work is to investigate the role of cavitation in transdermal insulin delivery. Fluorescently stained, soluble Actrapid insulin was placed on the surface of human skin-mimicking materials subjected to 265 kHz, 10% duty cycle focused ultrasound. A confocally and coaxially aligned 5 MHz broadband ultrasound transducer was used to detect cavitation. Two different skin models were used. The first model, 3% agar hydrogel, was insonated with a range of pressures (0.25-1.40 MPa peak rarefactional focal pressure-PRFP), with and without cavitation nuclei embedded within the agar at a concentration of 0.05% w/v. The second, porcine skin was insonated at 1.00 and 1.40 MPa PRFP. In both models, fluorescence measurements were used to determine penetration depth and concentration of delivered insulin. Results show that in agar gel, both insulin penetration depth and concentration only increased significantly in the presence of inertial cavitation, with up to a 40% enhancement. In porcine skin the amount of fluorescent insulin was higher in the epidermis of those samples that were exposed to ultrasound compared to the control samples, but there was no significant increase in penetration distance. The results underline the importance of instigating and monitoring inertial cavitation during transdermal insulin delivery.

Reference characterisation of sound speed and attenuation of the IEC agar-based tissue-mimicking material up to a frequency of 60 MHz.

To support the development of clinical applications of high-frequency ultrasound, appropriate tissue-mimicking materials (TMMs) are required whose acoustic properties have been measured using validated techniques. This paper describes the characterisation of the sound speed (phase velocity) and attenuation coefficient of the International Electrotechnical Commission (IEC) agar-based TMM over the frequency range 1 to 60 MHz. Measurements implemented a broadband through-transmission substitution immersion technique over two overlapping frequency ranges, with co-axially aligned 50 MHz centre-frequency transducers employed for characterisation above 15 MHz. In keeping with usual practice employed within the technical literature, thin acoustic windows (membranes) made of 12-µm-thick Mylar protected the TMM from water damage. Various important sources of uncertainty that could compromise measurement accuracy have been identified and evaluated through a combination of experimental studies and modelling. These include TMM sample thickness, measured both manually and acoustically, and the influence of interfacial losses that, even for thin protective membranes, are significant at the frequencies of interest. In agreement with previous reports, the attenuation coefficient of the IEC TMM exhibited non-linear frequency dependence, particularly above 20 MHz, yielding a value of 0.93 ± 0.04 dB cm(-1) MHz(-1) at 60 MHz, derived at 21 ± 0.5°C. For the first time, phase velocity, measured with an estimated uncertainty of ±3.1 m s(-1), has been found to be dispersive over this extended frequency range, increasing from 1541 m s(-1) at 1 MHz to 1547 m s(-1) at 60 MHz. This work will help standardise acoustic property measurements, and establishes a reference measurement capability for TMMs underpinning clinical applications at elevated frequencies.

Anomalous subsurface thermal behavior in tissue mimics upon near infrared irradiation mediated photothermal therapy.

Photothermal therapy using (Near Infrared) NIR region of EM spectrum is a fast emerging technology for cancer therapy. Different types of nanoparticles may be used for enhancing the treatment. Though the treatment protocols are developed based on experience driven estimated temperature increase in the tissue, it is not really known what spatiotemporal thermal behavior in the tissue is. In this work, this thermal behavior of tissue models is investigated with and without using nanoparticles. An increased temperature inside tissue compared to surface is observed which is counter intuitive from the present state of knowledge. It is shown from fiber level microstructure that this increased temperature leads to enhanced damage at the deeper parts of biomaterials. Nanoparticles can be utilized to control this temperature increase spatially. A multiple scattering based physical model is proposed to explain this counterintuitive temperature rise inside tissue. The results show promising future for better understanding and standardizing the protocols for photothermal therapy.

Characterizing an agar/gelatin phantom for image guided dosing and feedback control of high-intensity focused ultrasound.

The temperature dependence of an agar/gelatin phantom was evaluated. The purpose was to predict the material property response to high-intensity focused ultrasound (HIFU) for developing ultrasound guided dosing and targeting feedback. Changes in attenuation, sound speed, shear modulus and thermal properties with temperature were examined from 20°C to 70°C for 3 weeks post-manufacture. The attenuation decreased with temperature by a power factor of 0.15. Thermal conductivity, diffusivity and specific heat all increased linearly with temperature for a total change of approximately 16%, 10% and 6%, respectively. Sound speed had a parabolic dependence on temperature similar to that of water. Initially, the shear modulus irreversibly declined with even a slight increase in temperature. Over time, the gel maintained its room temperature shear modulus with moderate heating. A stable phantom was achieved within 2 weeks post-manufacture that possessed quasi-reversible material properties up to nearly 55°C.

Investigation of the effect of power ultrasound on the nucleation of water during freezing of agar gel samples in tubing vials.

Nucleation, as an important stage of freezing process, can be induced by the irradiation of power ultrasound. In this study, the effect of irradiation temperature (-2 °C, -3 °C, -4 °C and -5 °C), irradiation duration (0s, 1s, 3s, 5s, 10s or 15s) and ultrasound intensity (0.07 W cm(-2), 0.14 W cm(-2), 0.25 W cm(-2), 0.35 W cm(-2) and 0.42 W cm(-2)) on the dynamic nucleation of ice in agar gel samples was studied. The samples were frozen in an ethylene glycol-water mixture (-20 °C) in an ultrasonic bath system after putting them into tubing vials. Results indicated that ultrasound irradiation is able to initiate nucleation at different supercooled temperatures (from -5 °C to -2 °C) in agar gel if optimum intensity and duration of ultrasound were chosen. Evaluation of the effect of 0.25 W cm(-2) ultrasound intensity and different durations of ultrasound application on agar gels showed that 1s was not long enough to induce nucleation, 3s induced the nucleation repeatedly but longer irradiation durations resulted in the generation of heat and therefore nucleation was postponed. Investigation of the effect of ultrasound intensity revealed that higher intensities of ultrasound were effective when a shorter period of irradiation was used, while lower intensities only resulted in nucleation when a longer irradiation time was applied. In addition to this, higher intensities were not effective at longer irradiation times due to the heat generated in the samples by the heating effect of ultrasound. In conclusion, the use of ultrasound as a means to control the crystallization process offers promising application in freezing of solid foods, however, optimum conditions should be selected.

Comparative studies on the conformational change and aggregation behavior of irradiated carrageenans and agar by dynamic light scattering.

The conformational associative properties of kappa-, iota-, and lambda-carrageenan and agar with irradiation dose were studied by dynamic light scattering. The random scission of the carrageenans and agar by gamma irradiation resulted in the formation of polydispersed lower molecular weight fragments. At high doses, the system moves towards uniformity. Conformational change from coil to helix was observed in all carrageenans and agar at doses up to 100 kGy. The conformational change in lambda-carrageenan may be due to the irregular and hybrid structure of this polysaccharide. Only agar and lambda-carrageenan still undergo conformational transition at a high dose of 200 kGy. Gelation is observed for kappa-, iota-carrageenan up to a dose of 50 kGy while gelation is still observed at 100 kGy for agar. Increase in the hydrodynamic radius with decreasing temperatures for the non-irradiated carrageenans follows this order: lambda-carrageenan>kappa-carrageenan>iota-carrageenan. Slight increases in hydrodynamic radius were observed with irradiation.

Development of an eco-friendly agar extraction technique from the red seaweed Gracilaria lemaneiformis.

The red seaweed, Gracilaria lemaneiformis growing as an aquaculture bioremediator along the coasts of Liaodong Peninsula, China, was investigated for the agar production. An eco-friendly method called agar photobleaching extraction process was developed for the benefit of workers' health and safety of the environment. The native agar (NA), alkali-modified agar (AA), chemical-bleached agar (CA) and photobleached agar (PA), which were extracted using different processes, were evaluated for their physical and chemical properties. The PA showed most desirable performances in terms of gel strength, gelling temperature, sulfate content and 3,6-anhydro-l-galactose content. Among the different processed agars, PA gel strength was 1913 g/cm2, the highest among the different processed agars, which increased 8.6% on the basis of the AA. Further we applied this new technique to extract agars from Gracilaria asiatica, and similar results were obtained with that of G. lemaneiformis. This indicates that the agar photobleaching extraction process is a feasible method for Gracilaria species and has a potential application. During the whole agar photobleaching extraction process the pigment content of G. lemaneiformis declined gradually and the TOC concentration in photobleaching solution increased along with the increase in the irradiation time. The mechanism of agar photobleaching could be elucidated by the photolysis theory.

Inactivation of bacteria and yeasts on agar surfaces with high power Nd:YAG laser light.

Near infrared light from a high-powered, 1064 nm, Neodymium:Yttrium Aluminium Garnet (Nd:YAG) laser killed a variety of Gram-positive and Gram-negative bacteria and two yeasts, lawned on nutrient agar plates. A beam (cross-sectional area, 1.65 cm2) of laser light was delivered in 10 J, 8 ms pulses at 10 Hz, in a series of exposure times. For each microbial species, a dose/response curve was obtained of area of inactivation vs energy density (J cm-2). The energy density that gave an inactivation area (IA) equal to 50% of the beam area was designated the IA50-value and was plotted together with its 95% confidence limits. Average IA50-values were all within a threefold range and varied from 1768 J cm-2 for Serratia marcescens to 4489 J cm-2 for vegetative cells of Bacillus stearothermophilus. There were no systematic differences in sensitivity attributable to cell shape, size, pigmentation or Gram reaction. At the lowest energy densities where inactivation was achieved for the majority of organisms (around 2000 J cm-2), no effect was observed on the nutrient agar surface, but as the energy density was increased, a depression in the agar surface was formed, followed by localized melting of the agar.

The fungicidal effect of ultraviolet light on impression materials.

The effects of ultraviolet (UV) light on fungi and impression materials were tested. UV light (250 microW/cm2) killed most Candida organisms (10(3) cells/ml) within 5 minutes. UV light (8000 microW/cm2) killed most C. albicans (10(7) cells/ml) within 2 minutes of exposure. The effect of UV light on dimensional change and surface roughness of impression materials (irreversible hydrocolloid, agar, and silicone rubber) was tested. The results showed that neither dimensional change nor surface roughness of the impression materials were affected. The results of this study indicate that UV light disinfects impression materials that are contaminated with Candida organisms.

Alternation of the q-switched Nd:YAG laser and the cw argon laser for tunneling through organic material.

The rapidly alternating combination of Nd:YAG laser power of the optical break-down mode with cw energy of the argon laser ablates tissue. Blood agar provides a standard test medium as tissue substitute and permits to quantify the effect of various laser energy combinations to achieve optimal ablation. High wattage of the Nd:YAG laser provides destructive pressure that creates fissures which act as the light traps of a black body simulator for efficient cw argon laser energy conversion to pressure and kinetic energy. Within the fissure the deposited cw argon laser energy is directed by gradients toward the tissue surface so that deepening troughs or tunnels are formed by expelling tissue debris.

[Experimental studies of new Polish hydrogel dressing materials HDR]. / Badania doswiadczalne nowych polskich opatrunków hydrozelowych o symbolu HDR.

Recently the spectrum of dressings was enriched, incorporating the so-called hydrogel dressing, made by Geistlich Sons Ltd. and Byk Goldbin-Konstanz referred to as "Geliperm". In Poland, HDR hydrogel dressings' technology was launched by Institute of Radiative Technology, Lódz+ Polytechnic. This type of dressing is obtained by radiative cross-linking of hydrophilic polymers. The experimental studies of the new Polish hydrogel materials were accomplished at the Department of Experimental Surgery and Biomaterials Research, the Chair of traumatologic Surgery, Medical Academy of Wroclaw. These studies concerned three kinds of hydrogel dressings, different in composition and irradiation conditions. HDR-1 10% of polyvinylpyrrolidone+, 1.5% of agar, 1.5% of polyethylene glycol 300, irradiated with 30 kGy (gamma radiation of 60Co); HDR-1 with neomycin--formula as above plus neomycin sulfate (2.5%); HDR-2 6% of polyvinylpyrrolidone++, 1% of agar, 1.5% of polyethylene glycol 300, irradiated with 25-27 kGy (gamma radiation of 60Co). The usable properties of the HDR dressings approximate those of the West German products. Owing to the lab tests, biological and in vitro examinations we had performed, it was possible to state that aqueous extracts of the hydrogel dressings subjected to assessment did'nt exhibit hemolytical or toxic activities in cellular tests, at the same time lacking an irritating effect. They cause a minimal tissular reaction and accelerate the process of healing.