title: Molecular weight dependent tissue accumulation of dextrans: in vivo studies in rats.
abstract: The effects of molecular weight (M(r)) on the serum and urine pharmacokinetics and tissue distribution of dextrans, potential macromolecular carriers for drug delivery, were studied in rats. A single 5 mg/kg dose of fluorescein-labeled dextrans (FDs) with a M(r) of 4000 (FD-4), 20,000 (FD-20), 70,000 (FD-70), or 150,000 (FD-150) was administered into the tail vein of separate groups of rats. At different times after the administration of each FD, animals were sacrificed, and blood, urine, and various tissues were obtained. The concentrations of FDs in the samples were subsequently determined by using a sensitive and specific high performance size exclusions chromatographic method. Among the tissues studied, high accumulation of dextrans was found only in the liver (liver:serum AUC ratios < or = 29) and spleen (spleen:serum AUC ratios < or = 10), with high concentrations in these tissues persisting even at the last sampling time (96 h). In contrast, the serum concentrations of the studied FDs were not measurable beyond 12 h. The serum and urine kinetics and the liver, spleen, and kidney accumulation of FDs demonstrated a significant degree of M(r) dependency. The total and renal clearance of FDs consistently decreased with an increase in M(r). However, the effects of M(r) on the tissue accumulation of dextrans was tissue dependent. For the liver, the tissue:serum AUC ratios increased from 0.346 for FD-4 to 15.2 for FD-20 and 28.8 for FD-70, while a further increase in M(r) to 150 kDa (FD-150) resulted in lowering the ratio to 8.59 in this tissue. For the spleen, the ratios increased from 0.095 for FD-4 to 9.56 for FD-150.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: College of Pharmacy and Health Sciences, Drake University, Des Moines, IA 50311.
authors.forename: R
authors.initials: R
authors.lastname: Mehvar
authors.forename: M A
authors.initials: MA
authors.lastname: Robinson
authors.forename: J M
authors.initials: JM
authors.lastname: Reynolds
mesh_terms: D000818:Animals; D003911:Dextrans / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008099:Liver / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D003911:Dextrans