Effective drug delivery by PEGylated drug conjugates

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 wei...

Full description

Saved in:
Bibliographic Details
Published in:Advanced drug delivery reviews 2003-02, Vol.55 (2), p.217-250
Main Authors: Greenwald, Richard B., Choe, Yun H., McGuire, Jeffrey, Conover, Charles D.
Format: Article
Language:English
Subjects:
6-Mercaptopurine
Amphotericin B
Animals
Antibodies - administration & dosage
Antibodies - chemistry
Camptothecin
Clinical Trials as Topic
Daunorubicin, Ara-C
Doxorubicin
Drug Delivery Systems
Drug Design
Excipients - chemistry
Humans
Lysozyme
Oligonucleotides - administration & dosage
Oligonucleotides - chemistry
Paclitaxel
Pharmaceutical Preparations - administration & dosage
Pharmaceutical Preparations - chemistry
Poly (ethylene glycol)
Polyethylene Glycols - chemistry
Prodrugs
Prodrugs - administration & dosage
Prodrugs - chemistry
Proteins - administration & dosage
Proteins - chemistry
Tripartate prodrugs
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0169-409X
1872-8294
DOI:10.1016/S0169-409X(02)00180-1