Monitoring blood glucose concentration is a critical issue for diabetic patients. Many researches have been conducted aiming to achieve the continuous monitoring of blood glucose. There has been interest in transdermal drug delivery, that is, using skin as a port of entry into the body for the systemic delivery of therapeutic agents. Inversely people are trying to extract interested substances through the skin from the body. However, the applications of transdermal extraction are limited by low skin permeability. Specially, the outermost layer of the skin, the stratum corneum (SC), is the key barrier in the skin structure that limits the permeation through the skin. Different techniques including Reverse iontophoresis (RI) and low frequency sonophoresis (LFS) have been explored to overc...[ Read more ]

Monitoring blood glucose concentration is a critical issue for diabetic patients. Many researches have been conducted aiming to achieve the continuous monitoring of blood glucose. There has been interest in transdermal drug delivery, that is, using skin as a port of entry into the body for the systemic delivery of therapeutic agents. Inversely people are trying to extract interested substances through the skin from the body. However, the applications of transdermal extraction are limited by low skin permeability. Specially, the outermost layer of the skin, the stratum corneum (SC), is the key barrier in the skin structure that limits the permeation through the skin. Different techniques including Reverse iontophoresis (RI) and low frequency sonophoresis (LFS) have been explored to overcome this barrier and enhance the transdermal extraction.

RI involves an application of a small and constant current to the skin and enhance the delivery of ionized as well as unionized moieties. The mechanism of extraction involves either electromigration of charged species to the electrode of opposite polarity, or electroosmosis of polar neutral or zwitterionic molecules to the cathode.

Low frequency (20 kHz) ultrasound (US) has been shown to enhance transdermal transport of various molecules. A consensus on the mechanism has been reached that acoustic cavities, the formation and collapse of gaseous cavities which generated in the coupling medium, is responsible for LFS. The enhancement induced by LFS is determined by ultrasound parameters, frequency, intensity, duty cycle, application time, and distance of between the transducer and the skin.

In this research, the sonophoretic effect on transdermal glucose extraction together with RI is studied. RI is employed because it can not only enhance the permeation but also extract the interstitial glucose through the skin without causing any pain. Under the synergistic effect of LFS and RI, the permeation enhancement is supposed to be greater. Finally the extracted sample is analyzed by an enzyme biosensor.

Utilzing the commercial software, ANSYS, the finite element method (FEM) was used for analyzing the vibration mode of a flexible ultrasound transducer and determining the key parameters in the design.

In-vitro experiments are conducted using porcine skin to study the sonophoretic effect. With the pretreatment of LFS and RI, the glucose extraction rate is greater than that if only RI is used. The current of the detection signal is linearly proportional to the concentration in donor chamber no matter how long the application time is. In-vitro experiments also indicate that the longer the LFS excitation time is, the greater the enhancement is. Furthermore, the duration of the sonophoretic effect is also dependent on the LFS application time, the longer the LFS application time is, the longer duration of the effect lasts. This also implies that the skin should be treated by the LFS again after certain time of LFS application to keep the effect. The independence of the concentration makes the LFS more convenient for glucose monitoring when the concentration varies.

Keywords: glucose monitoring, non-invasive, sonophorestic effect, low frequency sonophoresis, reverse iontophoresis