Zinc oxide nanoparticles (ZnO NPs) are commonly used in sunscreens to reduce the risk of skin cancer by blocking
ultraviolet radiation. ZnO NPs absorption through the transdermal route may not cause high health risk as inhalation or
ingestion. However, in practical usage of sunscreens and cosmetics, ZnO NPs are topically applied to a large area of
skin with long periods hence the potential absorption amount of ZnO NPs is still need to be concerned. Therefore, if the
ZnO NPs are able the pass the barrier of normal skin, the pathways of transdermal delivery and the factors of
enhancements become important issues. In this work, multiphoton microscopy provides us a non-invasive visualization
of ZnO NPs in skin. Moreover, we quantitatively analyzed the enhancement of oleic acid and ethanol.
Due to the fact that photoluminance of ZnO NPs spectrally overlaps autofluorence from skin stratum corneum (SC) and
high turbidity of both ZnO NPs and SC, it is difficult to resolve the distribution of ZnO NPs in skin by using
fluorescence microscopy. In this work, the second harmonic generation (SHG) signals from ZnO NPs which double the
frequency of excitation source to characterize the delivery pathways and penetration depth in skin. Moreover, we
quantitatively compare the ZnO NPs delivery efficiency in normal skin and in skins with three chemically enhancing
conditions: ethanol, oleic acid and the combination of ethanol and oleic acid.
The indicator-dilution theory has been used for flow rate measurements in various imaging modalities, including magnetic resonance imaging, computed tomography and ultrasound. The experimental procedure generally involves the injection of a dose of indicator (i.e., the contrast agent), after which the concentration of the agent is monitored as a function of time; it is therefore also known as the time-intensity method. Although the time-intensity method has been widely applied to other imaging modalities, it has not been demonstrated with optoacoustic imaging. In this study, we experimentally test the hypothesis that quantitative blood flow measurements are feasible with the time-intensity based method in optoacoustic imaging. Gold nanospheres (broad band absorption spectrum peaks at 520 nm) were used as the optoacoustic contrast agent. The imaging system consisted of a frequency-doubled Nd:YAG laser operating at 532 nm for optical illumination, and an ultrasonic single crystal transducer with a center frequency of 3.5 MHz and a focal depth of 7 cm for detection. The volumetric flow rate ranged from 0.23 to 4.29 ml/sec, and the volume of the mixing chamber was from 30 to 80 ml. Results show good agreement between the measured mean transit times and the predicted time constants (correlation coefficient higher than 0.88), thus demonstrating the feasibility of the time-intensity based flow measurement technique. In addition to describing the method and experimental results, issues regarding the system sensitivity and estimation of the dilution transfer function are also discussed.
An interesting area of applying multiphoton fluorescence microscopy is in investigating the delivery of fluorescent nanoparticles (quantum dots) across biological barriers such as the skin. Fluorescence nanoparticles are nanometer in size and understanding the delivery mechanisms of these materials across the skin can be important in understanding the delivery of important biological macromolecules for therapeutic purposes. In addition, pathological diagnosis can be performed with the successful delivery of fluorescent nanoparticles.
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