PMID- 17706831
OWN - NLM
STAT- MEDLINE
DCOM- 20071105
LR  - 20181201
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Linking)
VI  - 122
IP  - 3
DP  - 2007 Oct 8
TI  - Rescue of SCID murine ischemic hindlimbs with pH-modified 
      rhbFGF/poly(DL-lactic-co-glycolic acid) implants.
PG  - 331-7
AB  - Site-specific controlled release of biologically active angiogenic growth factors 
      such as recombinant human basic fibroblast growth factor (rhbFGF) is a promising 
      approach to improve collateral circulation in patients suffering from ischemic 
      heart disease or peripheral vascular disease. Previously, we demonstrated 
      stabilization of rhbFGF encapsulated in injectable poly(DL-lactic-co-glycolic 
      acid) (PLGA) millicylindrical implants upon co-incorporation of Mg(OH)2 to raise 
      the microclimate pH in the polymer. The purpose of this study was to compare 
      stabilized (S; +Mg(OH)2+other stabilizers), partially stabilized (PS; 
      -Mg(OH)2+other stabilizers), unstabilized (US; no stabilizers), and blank (B) 
      PLGA-encapsulated rhFGF formulations to promote angiogenesis in SCID mice. 
      Following 4 weeks subcutaneous implantation at a 0.1 microg dose in healthy 
      animals, the S group exhibited significantly higher blood vessel density (62+/-17 
      vessels/mm2) compared with PS, US, and B groups (11+/-2*, 17+/-7*, and 3+/-1** 
      respectively) (* p<0.05; ** p<0.01). Furthermore, the S group developed a thicker 
      granulation layer at the tissue/implant interface relative to the other groups 
      (39+/-7 vs 25+/-2**, 21+/-1***, and 12+/-1 microm*** respectively) (*** p<0.001). 
      After 6 weeks implantation in mice with ischemic hindlimbs, the S group implants 
      also markedly augmented both limb reperfusion (87+/-14%) and limb survival (5/5), 
      whereas ischemic limbs did not recover in PS, US and B groups. Stabilized rhbFGF 
      incorporated in pH modified PLGA millicylinders effectively promotes 
      site-directed in vivo angiogenesis and also enables preservation of ischemic 
      hindlimb function.
FAU - Zhong, Yanqiang
AU  - Zhong Y
AD  - Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 
      48109, USA.
FAU - Zhang, Li
AU  - Zhang L
FAU - Ding, Amy G
AU  - Ding AG
FAU - Shenderova, Anna
AU  - Shenderova A
FAU - Zhu, Gaozhong
AU  - Zhu G
FAU - Pei, Ping
AU  - Pei P
FAU - Chen, Ruth R
AU  - Chen RR
FAU - Mallery, Susan R
AU  - Mallery SR
FAU - Mooney, David J
AU  - Mooney DJ
FAU - Schwendeman, Steven P
AU  - Schwendeman SP
LA  - eng
GR  - CA 95901/CA/NCI NIH HHS/United States
GR  - HL 68345/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070523
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Angiogenesis Inducing Agents)
RN  - 0 (Drug Carriers)
RN  - 0 (Polymers)
RN  - 0 (Recombinant Proteins)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 62031-54-3 (Fibroblast Growth Factors)
SB  - IM
MH  - Angiogenesis Inducing Agents/administration & dosage/pharmacology/*therapeutic 
      use
MH  - Animals
MH  - Disease Models, Animal
MH  - Drug Carriers/*chemistry
MH  - Fibroblast Growth Factors/administration & dosage/pharmacology/*therapeutic use
MH  - Hindlimb/*blood supply/pathology
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Ischemia/*drug therapy/pathology
MH  - Lactic Acid/*chemistry
MH  - Male
MH  - Mice
MH  - Mice, SCID
MH  - Necrosis
MH  - Neovascularization, Physiologic/drug effects
MH  - Polyglycolic Acid/*chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Polymers/*chemistry
MH  - Recombinant Proteins/chemistry
MH  - Regional Blood Flow/drug effects
EDAT- 2007/08/21 09:00
MHDA- 2007/11/06 09:00
CRDT- 2007/08/21 09:00
PHST- 2007/04/02 00:00 [received]
PHST- 2007/05/08 00:00 [revised]
PHST- 2007/05/11 00:00 [accepted]
PHST- 2007/08/21 09:00 [pubmed]
PHST- 2007/11/06 09:00 [medline]
PHST- 2007/08/21 09:00 [entrez]
AID - S0168-3659(07)00239-8 [pii]
AID - 10.1016/j.jconrel.2007.05.016 [doi]
PST - ppublish
SO  - J Control Release. 2007 Oct 8;122(3):331-7. doi: 10.1016/j.jconrel.2007.05.016. 
      Epub 2007 May 23.