Over the last decade, polymer micelles and nanoparticles attracted an increasing interest in drug research because they can be used as efficient drug delivery systems 1 . Nanoparticles are submicron-sized polymeric colloidal particles with a therapeutic agent of interest encapsulated within their polymeric matrix 2 . The addition of an amphiphilic block copolymer made up of poly(ethylene oxide) and an aliphatic polyester, such as poly(ε-caprolactone) (PCL) or polylactide (PLA), to the formulation permits to take advantage of the protein repellent properties of PEO to increase the time live of the nanoparticles in the vascular residence.The use of polymeric nanoparticles for the delivery of complex antigens, the combination of antigens, and genetic vaccines makes them one of the most promising strategies for oral vaccination 3 . Polymeric carriers protect antigens against degradation and inactivation in the harsh gastro-intestinal environment and have the ability to enhance their transmucosal transport. When these copolymers have a targeting agent, the biodistribution of polymeric micelles can be modulated and can induce specific cellular uptake by receptor-mediated endocytosis.

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A source of urea in the skin, unrelated to the concentration circulating in the blood, was strongly suggested by extracted urea flux observed over time and by the Raman spectroscopy. This "urea reservoir" must be removed before systemic urea levels can be non-invasively monitored by reverse iontophoresis.

Purpose. Reverse iontophoresis is an alternative to blood sampling for the monitoring of endogenous molecules. Here, the potential of the technique to measure urea and potassium levels non-invasively, and to track their concentrations during hemodialysis, has been examined. Materials and Methods. In vitro experiments were performed to test (a) a series of subdermal urea and potassium concentrations typical of the pathophysiologic range, and (b) a decreasing profile of urea and potassium subdermal concentrations to mimic those which are observed during hemodialysis. Results. (a) After 60Y120 min of iontophoresis, linear relationships (p<0.05) were established between both urea and potassium fluxes and their respective subdermal concentrations. The determination coefficients were above 0.9 after 1 h of current passage using sodium as an internal standard. (b) Reverse iontophoretic fluxes of urea and K + closely paralleled the decay of the respective concentrations in the subdermal compartment, as would occur during a hemodialysis session. Conclusions. These in vitro experiments demonstrate that urea and potassium can be quantitatively and proportionately extracted by reverse iontophoresis, even when the subdermal concentrations of the analytes are varying with time. These results suggest the non-invasive monitoring of urea and potassium to diagnose renal failure and during hemodialysis is feasible, and that in vivo measurements are warranted.