PMID- 20005271
OWN - NLM
STAT- MEDLINE
DCOM- 20100920
LR  - 20210212
IS  - 1872-8294 (Electronic)
IS  - 0169-409X (Linking)
VI  - 62
IP  - 2
DP  - 2010 Feb 17
TI  - Do HPMA copolymer conjugates have a future as clinically useful nanomedicines? A 
      critical overview of current status and future opportunities.
PG  - 272-82
LID - 10.1016/j.addr.2009.12.005 [doi]
AB  - N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer conjugates containing 
      doxorubicin designed in the late 1970s/early 1980s as anticancer polymer 
      therapeutics were the first synthetic polymer-based anticancer conjugates to 
      enter clinical trial beginning in 1994. Early clinical results were promising, 
      confirming activity in chemotherapy refractory patients and the safety of HPMA 
      copolymers as a new polymer platform in this setting. Subsequent Phase I/II 
      trials have investigated conjugates containing paclitaxel (PNU 166945), 
      camptothecin (PNU 166148) (both failed in clinical trials underlining the 
      importance of rational design), and most recently HPMA-copolymer platinates 
      (AP5280 and then AP5346-ProLindac(TM)) entered Phase II clinical development. 
      There are a growing array of second generation HPMA copolymer-based systems 
      involving combination therapy, incorporating putative targeting ligands, having 
      an ever more complex architecture, and both drug and protein conjugates are being 
      proposed as novel treatments for diseases other than cancer. Despite their 
      promise, and the success of polymeric drugs and polymer-protein conjugates, no 
      polymer-drug conjugate (HPMA copolymer-based or otherwise) has yet entered 
      routine clinical use. It is timely to reflect on the progress made over the last 
      30 years, the relative merits of HPMA copolymers as a platform compared to other 
      polymeric carriers, and comment on their future potential as polymer-based 
      nanomedicines into the 21st century in comparison with the many alternative 
      strategies now emerging for creation of nanopharmaceuticals.
CI  - Copyright 2009 Elsevier B.V. All rights reserved.
FAU - Duncan, Ruth
AU  - Duncan R
AD  - School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10 
      3AT, UK. Profruthduncan@btinternet.com
FAU - Vicent, Maria J
AU  - Vicent MJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20091211
PL  - Netherlands
TA  - Adv Drug Deliv Rev
JT  - Advanced drug delivery reviews
JID - 8710523
RN  - 0 (Acrylamides)
RN  - 0 (Polymers)
RN  - R3F262Z4E0 (N-(2-hydroxypropyl)methacrylamide)
SB  - IM
MH  - Acrylamides/chemistry/*therapeutic use
MH  - Animals
MH  - Forecasting
MH  - Humans
MH  - Nanomedicine/*trends
MH  - Polymers/chemistry/*therapeutic use
RF  - 58
EDAT- 2009/12/17 06:00
MHDA- 2010/09/21 06:00
CRDT- 2009/12/17 06:00
PHST- 2009/11/27 00:00 [received]
PHST- 2009/11/30 00:00 [accepted]
PHST- 2009/12/17 06:00 [entrez]
PHST- 2009/12/17 06:00 [pubmed]
PHST- 2010/09/21 06:00 [medline]
AID - S0169-409X(09)00389-5 [pii]
AID - 10.1016/j.addr.2009.12.005 [doi]
PST - ppublish
SO  - Adv Drug Deliv Rev. 2010 Feb 17;62(2):272-82. doi: 10.1016/j.addr.2009.12.005. 
      Epub 2009 Dec 11.