In vitro and in vivo evaluation of hydrophilic dendronized linear polymers.
Rigid-rod dendronized linear polymers consisting of a poly(4-hydroxystyrene) backbone and fourth-generation polyester dendrons were evaluated in vitro and in vivo to determine their suitability as drug delivery vectors. Cytotoxicity assays indicated that the polymers were well tolerated by cells in vitro. Biodistribution studies of the polymers in both nontumored and tumored mice revealed that as for random coil linear polymers, renal clearance was a function of polymer size, with significant urinary excretion observed for a 67 kDa dendronized polymer. High accumulation in organs of the reticuloendothelial system was exhibited by a dendronized polymer with a very high molecular weight (M(n) = 1740 kDa), but was not as significant for smaller polymers with M(n) = 67 kDa and M(n) = 251 kDa. The rank order for tumor accumulation of the polymers on a percent injected dose per gram tumor basis was 251 kDa approximately 1740 kDa > 67 kDa. These data will help guide the selection of highly functionalizable rigid-rod dendronized polymers with pharmacokinetic properties appropriate for use as drug carriers.
Lee
Cameron C
CC
Center for New Directions in Organic Synthesis, Department of Chemistry, University of California, Berkeley, California 94720-1460, USA.
Yoshida
Masaru
M
Fréchet
Jean M J
JM
Dy
Edward E
EE
Szoka
Francis C
FC
D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D008970:Molecular Weight; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D011108:Polymers