Synthesis, characterization, and in vivo disposition of iodinatable polyethylene glycol derivatives: Differences in vivo as a function of chain length

Abstract

and P h a r m a c e u t i c a l Chemistry U n i v e r s i t y of C a l i f o r n i a San F r a n c i s c o , C a l i f o r n i a 94143 SUMMARY were p r e p a r e d f o r u s e as model h y d r o p h i l i c d r u g s . P o l y e t h y l e n e g l y c o l diamine 6000 was coupled t o m e t h y l l -h y d r o x y b e n z i m i d a t e , and PEG 1900-and PEG 5000monomethyl e t h e r s were c o u p l e d t o t y r a m i n e and h i s t a m i n e . The d e r i v a t i v e s underwent f a c i l e i o d i n a t i o n w i t h t h e chloramine-T r e a c t i o n and were s t a b l e under a wide range of c o n d i t i o n s . The l a r g e r d e r i v a t i v e s showed r a p i d r e n a l c l e a r a n c e , b u t t h e 1900 MW compounds underwent s i g n i f i c a n t c l e a r a n c e v i a t h e b i l e .

A single dose of doxorubicin-functionalized bow-tie dendrimer cures mice bearing C-26 colon carcinomas

“…The radioiodinated phenols used for these biodistribution experiments were located on the periphery of the dendron opposite to the dendron with the attached PEO chains. Because polymers containing iodinated phenols are known to exhibit high levels of liver uptake (19,24), these results indicate that more branched bow ties offer better steric protection of molecules located on the periphery of the opposite dendron (Fig. 1).…”

The influence of polymer topology on pharmacokinetics: Differences between cyclic and linear PEGylated poly(acrylic acid) comb polymers

“…[21] Polymer solutions (200 μL) at a dose of approximately 50 mg/kg were administered intravenously via the tail vein to 6–8 week old BALB/c female mice. The mice were sacrificed at seven different time points (three mice per group) ranging from 5 min to 48 h postinjection for biodistribution analyses.…”

Functionalized Poly(ethylene glycols) for Preparation of Biologically Relevant Conjugates

“…The higher reactivity of primary amino-PEG (4) compared to hydroxy-terminated PEG in nucleophilic substitution reactions makes it a widely used derivative for preparation of various bioconjugates. Lowmolecular weight drugs, cofactors, and other ligands (8,(58)(59)(60)(61), peptides (62), glycoproteins (63), and surfaces of biomaterials (64, 65) have been interlinked with amino-PEG through amide, sec-amine, urea, thiourea, and urethane, all stable in vivo linkages. Formation of an amide linkage with 4 was found to be a particularly useful reaction, which can be driven to completion under very mild conditions (3).…”

“…However, good preservation of biological activity of the conjugates was usually observed (52, 108). In addition to modification of polypeptide materials, the reagent was also used for preparation of mPEG-DSPE conjugates (111,112) and linking various small ligands to PEG (60,109,113). It is pertinent to note that the aliphatic urethane linkage formed as a result of primary amino-containing ligand attachment to 11 is extremely stable under a variety of physiological conditions and shows very little breakdown in various buffers pH 2-11 (60).…”