G. Rao et al., REVERSE IONTOPHORESIS - DEVELOPMENT OF A NONINVASIVE APPROACH FOR GLUCOSE MONITORING, Pharmaceutical research, 10(12), 1993, pp. 1751-1755
Solvent flow generated during iontophoresis can be used to convect neu
tral molecules through the skin, thereby greatly enhancing their flux.
This concept was exploited to realize noninvasive glucose measurement
by its iontophoretic extraction from the subcutaneous tissue. The hyp
othesis was tested in vitro using hairless mouse skin. The dermal surf
ace was bathed with a glucose solution; chambers on the epidermal surf
ace housed the current delivery electrodes. Iontophoresis (at 0.36 mA/
cm2) was performed for 2 hr, at the end of which the solutions in cont
act with the electrodes were analyzed. The amount extracted was propor
tional to the glucose solution concentration bathing the dermis. Highe
r radioactivity levels were found at the anode than at the cathode, po
ssibly because of glucose metabolism during its outward transport acro
ss the skin. Glucose biotransformation results in negatively charged m
etabolites which migrate to the anode. Two sensitive glucose sensors w
ere developed; one was selective for glucose, the other for glucose an
d related compounds. Both sensors indicated the presence of glucose at
the cathode but an abnormally high value was also recorded at the ano
de. This signal, however, was not due to glucose but rather to electro
active ascorbate withdrawn from the skin. Finally, a system has been d
eveloped with which glucose can be extracted noninvasively from the su
bcutaneous tissue and unambiguously measured. Whether iontophoretic gl
ucose sampling in vivo will be equally successful remains to be answer
ed.