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SONOPHORESIS OF SKIN WITH FLUORESCENT POLYSTYRENE MICROSPHERES Modern methods of drug delivery have many disadvantages. Intravenous drug delivery often involves patient fear and non-compliance. Long-term oral delivery often results in liver damage since, to overcome first-pass metabolism, oral doses are taken in very high amounts. Oral drug delivery, even for the few drugs that survive gastrointestinal degradation, is not well-controlled because fluctuations in the absorption rates of the digestive system vary the amount of drug actually entering the blood stream. An appealing alternative to intravenous and oral drug delivery is transdermal drug delivery, a painless method with added benefits of possible sustained controlled release and extraction of fluid for samples. Transdermal drug delivery is hindered by the impermeability of the stratum corneum, the outermost layer of the skin. Different methods to overcome this barrier are currently being studied. One of the most promising is sonophoresis, the application of ultrasound to the skin. Sonophoresis enhances skin permeability for a prolonged period of time with no apparent harmful side effects. Unfortunately, its mechanisms are not well understood. The primary sonophoresis mechanism believed to increase skin permeability is transient cavitation. Pressure from ultrasound and the skin forces cavitation bubbles to collapse in on themselves, forming microjets that shoot into the skin like needles, disrupting the stratum corneum and delivering drugs from the liquid medium. Another possible mechanism is physical impact of the particles with the ultrasound transducer, which vibrates at a speed of O(100)m/s. The particles are accelerated and shot into the skin at high velocities. My project involved sonicating skin with fluorescent polystyrene microspheres (~2um and 5um diameters) and determining the number of particles to reach various depths in the stratum corneum by standard tape stripping of the skin and counting the particles under a fluorescent microscope. Comparisons of these results may help in the analysis of sonophoresis mechanisms. Transient cavitation should deliver smaller particles most efficiently because more particles would become trapped in the microjet. Particle delivery from impact with the transducer should peak since larger particles encounter more resistance from the skin but smaller particles have less momentum. Experiments showed that 2mm microspheres entered the stratum corneum at higher percentages, at all depths, than the 5mm microspheres. While this may suggest that microjets are more responsible for the rise in skin permeability than the impact of the transducer, more particle sizes must be studied before the results can be reliably analyzed.
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