The current review presents an update of
drug delivery using poly(
ethylene glycol) (PEG), that focuses on recent developments in both
protein and organic drugs. Certainly the past 10 years has resulted in a renaissance of the field of PEG
drug conjugates, initiated by the use of higher molecular weight PEGs (M(w)>20,000), especially 40,000 which is estimated to have a plasma circulating t(1/2) of approximately 10 h in mice. This recent
resuscitation of small organic molecule delivery by high molecular weight PEG conjugates was founded on meaningful in vivo testing using established
tumor models, and has led to a clinical candidate,
PEG-camptothecin (
PROTHECAN), an
ester based
prodrug currently in phase II trials. Additional applications of high molecular weight PEG
prodrug strategies to amino containing drugs are presented: similar tripartate systems based on lower M(w) PEG and their use with
proteins is expounded on. The modification of a benzyl elimination tripartate
prodrug specific for
mercaptans is presented, and its successful application to
6-mercaptopurine giving a water soluble formulation is discussed. Recent novel PEG
oligonucleotides and
immunoconjugates are also covered. Clinical results of FDA approved PEGylated
proteins are also presented.