Pharmacokinetic Analysis And Tissue Distribution Characteristics Of Macromolecules

The pharmacokinetic characteristics are generally determined by the physicochemical properties of the molecule such as the size, molecular weight, and surface charge.3 Moreover, specific interactions such as ligand-receptor or antibody-antigen have a major effect on the characteristics of the molecule after intravenous injection.4 The former factors are closely related to passive targeting, and the latter factors are closely related to active targeting. Figure 4.2 summarizes the

0.01 0.1 1 10 Urinary excretion clearance (ml/h)

0.01 0.1 1 10 Urinary excretion clearance (ml/h)

FIGURE 4.2 Effect of physicochemical characteristics of macromolecules on their hepatic uptake and urinary excretion in mice. The number in parenthesis is the molecular weight. Abbreviations in this figure are as follows: SOD, superoxide dismutase; Man-SOD, mannosylated superoxide dismutase; Gal-SOD, galactosy-lated superoxide dismutase; PEG-SOD, pegylated superoxide dismutase; Cat-BSA, cationized bovine serum albumin; PEG-CAT, pegylated catalase; ODN, oligonucleotide. (From Kawabata, K., Takakura, Y., and Hashida, M., Pharm. Res., 12, 1995; Hashida, M., et al., J. Control. Release, 41,1996; Fujita, T., et al., J. Pharmacol. Exp. Theor., 263, 1992; Yamasaki, Y., et al., J. Pharmacol. Exp. Theor., 301, 2002; Yabe, Y., et al., J. Pharmacol. Exp. Theor., 289, 1999.)

effect of size, charge, and ligand modification of macromolecules on hepatic uptake clearance and urinary excretion clearance that essentially decide the pharmacokinetic properties of the macro-molecule. Understanding the effect of the physicochemical properties of macromolecules on their tissue distribution allows theoretical design delivery systems, involving nanocarriers.

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