PMID- 19671438
OWN - NLM
STAT- MEDLINE
DCOM- 20100202
LR  - 20220309
IS  - 1872-8294 (Electronic)
IS  - 0169-409X (Linking)
VI  - 61
IP  - 13
DP  - 2009 Nov 12
TI  - PEG conjugates in clinical development or use as anticancer agents: an overview.
PG  - 1177-88
LID - 10.1016/j.addr.2009.02.010 [doi]
AB  - During the almost forty years of PEGylation, several antitumour agents, either 
      proteins, peptides or low molecular weight drugs, have been considered for 
      polymer conjugation but only few entered clinical phase studies. The results from 
      the first clinical trials have shared and improved the knowledge on 
      biodistribution, clearance, mechanism of action and stability of a polymer 
      conjugate in vivo. This has helped to design conjugates with improved features. 
      So far, most of the PEG conjugates comprise of a protein, which in the native 
      form has serious shortcomings that limit the full exploitation of its therapeutic 
      action. The main issues can be short in vivo half-life, instability towards 
      degrading enzymes or immunogenicity. PEGylation proved to be effective in 
      shielding sensitive sites at the protein surface, such as antigenic epitopes and 
      enzymatic degradable sequences, as well as in prolonging the drug half-life by 
      decreasing the kidney clearance. In this review PEG conjugates of proteins or low 
      molecular weight drugs, in clinical development or use as anticancer agents, will 
      be taken into consideration. In the case of PEG-protein derivatives the most 
      represented are depleting enzymes, which act by degrading amino acids essential 
      for cancer cells. Interestingly, PEGylated conjugates have been also considered 
      as adjuvant therapy in many standard anticancer protocols, in this regard the 
      case of PEG-G-CSF and PEG-interferons will be presented.
FAU - Pasut, Gianfranco
AU  - Pasut G
AD  - Department of Pharmaceutical Sciences, University of Padua, via Marzolo 5, 35100 
      Padova, Italy. gianfranco.pasut@unipd.it
FAU - Veronese, Francesco M
AU  - Veronese FM
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20090809
PL  - Netherlands
TA  - Adv Drug Deliv Rev
JT  - Advanced drug delivery reviews
JID - 8710523
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Drug Carriers)
RN  - 0 (Peptides)
RN  - 0 (Proteins)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*administration & dosage/pharmacokinetics/pharmacology
MH  - Clinical Trials as Topic
MH  - Drug Carriers/*chemistry
MH  - Drug Design
MH  - Drug Stability
MH  - Humans
MH  - Neoplasms/drug therapy
MH  - Peptides/administration & dosage/pharmacokinetics/pharmacology
MH  - Polyethylene Glycols/*chemistry
MH  - Proteins/administration & dosage/pharmacokinetics/pharmacology
RF  - 107
EDAT- 2009/08/13 09:00
MHDA- 2010/02/03 06:00
CRDT- 2009/08/13 09:00
PHST- 2009/01/07 00:00 [received]
PHST- 2009/02/14 00:00 [accepted]
PHST- 2009/08/13 09:00 [entrez]
PHST- 2009/08/13 09:00 [pubmed]
PHST- 2010/02/03 06:00 [medline]
AID - S0169-409X(09)00239-7 [pii]
AID - 10.1016/j.addr.2009.02.010 [doi]
PST - ppublish
SO  - Adv Drug Deliv Rev. 2009 Nov 12;61(13):1177-88. doi: 10.1016/j.addr.2009.02.010. 
      Epub 2009 Aug 9.