Molecular weight dependence on bioavailability of FITC-dextran after administration of self-dissolving micropile to...

Self-dissolving micropiles (SDMPs) have been evaluated with macromolecular drugs like insulin and erythropoietin as a new percutaneous drug delivery system. To study the molecular weight dependence on the absorption of macromolecular drugs through the skin after administration of SDMPs, four kinds of SDMP were prepared using fluorescein isothiocyanate-labeled dextrans (FDs) having a molecular weight of 10, 20, 40, and 70 kDa.

In in vitro release experiments there were no significant differences on their release rates in the four SDMPs. The dependence of molecular weight of FD on the permeability coefficient was studied in the in vitro permeation experiment. Histological study on the skin after administration of FD SDMP (5.0 mg/kg) to rat was performed for 24 hours. In vivo experiment using rats resulted in slower absorption rate of FD-40 and FD-70 SDMP (5.0 mg/kg).

The permeability coefficient was 4.59, 4.69, 3.38, and 1.43 x 10(-4) cm/h for FD-10, 20, 40, and 70, respectively. Histological examination showed that yellow color was still observed at 6 h after administration of FD-40, and FD-70 showed yellow color even at 24 h. Bioavailabilities of FDs from SDMP were 99.4 +/- 6.93%, 88.3 +/- 7.05%, 45.7 +/- 4.77%, and 16.0 +/- 1.15% for FD-10, 20, 40, and 70, and the dependency on molecular weight dependence was clearly observed.

These observations supported that bioavailabilities of FD from SDMP decreased as the molecular weight of FD increased to more than 40 kDa.