PMID- 24126220
OWN - NLM
STAT- MEDLINE
DCOM- 20140825
LR  - 20211021
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Print)
IS  - 0168-3659 (Linking)
VI  - 172
IP  - 3
DP  - 2013 Dec 28
TI  - Sustained delivery of a HIF-1 antagonist for ocular neovascularization.
PG  - 625-33
LID - S0168-3659(13)00838-9 [pii]
LID - 10.1016/j.jconrel.2013.10.008 [doi]
AB  - Doxorubicin (DXR) and daunorubicin (DNR) inhibit hypoxia-inducible factor-1 
      (HIF-1) transcriptional activity by blocking its binding to DNA. Intraocular 
      injections of DXR or DNR suppressed choroidal and retinal neovascularization 
      (NV), but also perturbed retinal function as demonstrated by electroretinograms 
      (ERGs). DXR was conjugated to novel copolymers of branched polyethylene glycol 
      and poly(sebacic acid) (DXR-PSA-PEG3) and formulated into nanoparticles that when 
      placed in aqueous buffer, slowly released small DXR-conjugates. Intraocular 
      injection of DXR-PSA-PEG3 nanoparticles (1 or 10 mug DXR content) reduced 
      HIF-1-responsive gene products, strongly suppressed choroidal and retinal NV, and 
      did not cause retinal toxicity. In transgenic mice that express VEGF in 
      photoreceptors, intraocular injection of DXR-PSA-PEG3 nanoparticles (10 mug DXR 
      content) suppressed NV for at least 35 days. Intraocular injection of 
      DXR-PSA-PEG3 nanoparticles (2.7 mg DXR content) in rabbits resulted in sustained 
      DXR-conjugate release with detectable levels in aqueous humor and vitreous for at 
      least 105 days. This study demonstrates a novel HIF-1-inhibitor-polymer conjugate 
      formulated into controlled-release particles that maximizes efficacy and duration 
      of activity, minimizes toxicity, and provides a promising new chemical entity for 
      treatment of ocular NV.
CI  - (c) 2013.
FAU - Iwase, Takeshi
AU  - Iwase T
AD  - Department of Ophthalmology, Baltimore, USA; Department of Neuroscience, 
      Baltimore, USA.
FAU - Fu, Jie
AU  - Fu J
FAU - Yoshida, Tsunehiko
AU  - Yoshida T
FAU - Muramatsu, Daisuke
AU  - Muramatsu D
FAU - Miki, Akiko
AU  - Miki A
FAU - Hashida, Noriyasu
AU  - Hashida N
FAU - Lu, Lili
AU  - Lu L
FAU - Oveson, Brian
AU  - Oveson B
FAU - Lima e Silva, Raquel
AU  - Lima e Silva R
FAU - Seidel, Christopher
AU  - Seidel C
FAU - Yang, Ming
AU  - Yang M
FAU - Connelly, Sheila
AU  - Connelly S
FAU - Shen, Jikui
AU  - Shen J
FAU - Han, Bing
AU  - Han B
FAU - Wu, Mingsheng
AU  - Wu M
FAU - Semenza, Gregg L
AU  - Semenza GL
FAU - Hanes, Justin
AU  - Hanes J
FAU - Campochiaro, Peter A
AU  - Campochiaro PA
LA  - eng
GR  - R01 EY012609/EY/NEI NIH HHS/United States
GR  - EY012609/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20131012
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 80168379AG (Doxorubicin)
RN  - ZS7284E0ZP (Daunorubicin)
SB  - IM
MH  - Animals
MH  - Antibiotics, Antineoplastic/*administration & dosage/pharmacokinetics/therapeutic 
      use
MH  - Daunorubicin/*administration & dosage/pharmacokinetics/therapeutic use
MH  - Delayed-Action Preparations/*chemistry
MH  - Doxorubicin/*administration & dosage/pharmacokinetics/therapeutic use
MH  - Hypoxia-Inducible Factor 1/*antagonists & inhibitors/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Nanoparticles/chemistry
MH  - Polyethylene Glycols/chemistry
MH  - Rabbits
MH  - Retina/*drug effects/metabolism/pathology
MH  - Retinal Neovascularization/*drug therapy/metabolism/pathology
PMC - PMC3871855
MID - NIHMS531937
OTO - NOTNLM
OT  - Age-related macular degeneration
OT  - Angiogenesis
OT  - Diabetic retinopathy
OT  - Nanoparticles
EDAT- 2013/10/16 06:00
MHDA- 2014/08/26 06:00
PMCR- 2014/12/28
CRDT- 2013/10/16 06:00
PHST- 2013/08/06 00:00 [received]
PHST- 2013/09/30 00:00 [revised]
PHST- 2013/10/05 00:00 [accepted]
PHST- 2013/10/16 06:00 [entrez]
PHST- 2013/10/16 06:00 [pubmed]
PHST- 2014/08/26 06:00 [medline]
PHST- 2014/12/28 00:00 [pmc-release]
AID - S0168-3659(13)00838-9 [pii]
AID - 10.1016/j.jconrel.2013.10.008 [doi]
PST - ppublish
SO  - J Control Release. 2013 Dec 28;172(3):625-33. doi: 10.1016/j.jconrel.2013.10.008. 
      Epub 2013 Oct 12.