ABSORPTION CHARACTERISTICS OF DEXTRANS WITH DIFFERENT MOLECULAR-WEIGHTS FROM THE LIVER SURFACE-MEMBRANE IN RATS - IMPLICATIONS FOR TARGETING TO THE LIVER

We examined the importance of molecular weight on the absorption from the liver surface in rats using fluorescein isothiocyanate-dextrans (F Ds) with molecular weights of 4,400 (FD-4), 9,300 (FD-10), 40,500 (FD- 40) or 69,000 (FD-70). After application of FDs (5 mg) to the rat live r surface employing a cylindrical glass cell (i.d. 9 mm), each FD appe ared gradually in the plasma, and the in vivo behavior was explained b y two-compartment model with first-order absorption. The absorption ra tios of FDs from the rat liver surface at 6 h, calculated from the amo unt recovered from the glass cell, decreased with an increase in the m olecular weight (44.5% for FD-4, 29.3% for FD-10, 5.1% for FD-40 and 2 .2% for FD-70). A linear relationship was observed between the absorpt ion rate constant and the reciprocal value with square root of molecul ar weight of the model compounds. The Limit of absorption from the rat liver surface was extrapolated to be at a molecular weight of 70,000. Furthermore, absorbed FDs were accumulated in the liver, as high live r/plasma concentration ratio as compared with that of i.v. administrat ion. We clarified the molecular weight dependence of drug absorption f rom the liver surface in rats. Moreover, the liver surface application appeared to be a promising route with enhancing the efficacy of drug targeting to the liver.