title: Liposomal angiogenic peptides for ischemic limb perfusion: comparative study between different administration methods.
abstract: BACKGROUND
  We investigated the therapeutic effectiveness of PEGylated liposomes loaded with angiogenic peptides for treating hindlimb ischemia.
  
  
  METHODS
  Rats received a femoral artery occlusion. Red blood cells collected from the animals were labeled with technetium-99m. Limb perfusion gamma imaging was performed. PEGylated liposomes loaded with angiogenic peptides were administered intra-arterially. Technetium-99m red blood cell imaging was repeated 1 week later. The animals were sacrificed the next day. The expression of angiogenic proteins was studied. Later, changes in limb perfusion after intra-arterial infusion versus intra-muscular injection were also compared to determine the therapeutic effectiveness of different administration methods.
  
  
  RESULTS
  Femoral artery occlusion dramatically reduced ischemic limb perfusion (by an average of 69%, compared to contralateral limb). This was not different among groups (p > 0.05). Liposomes loaded with angiogenic peptides significantly improved ischemic limb perfusion, compared to controls (210% of baseline, versus 100% of baseline in control; p < 0.05 versus controls). The enhanced ischemic limb perfusion was accompanied by an increased expression of CD 31 (an average of 1.6-fold increase of controls; p < 0.05). The liposomes or peptides treatment alone did not affect ischemic perfusion (liposomes alone: 100% of baseline; peptides alone: 120% of baseline; p > 0.05 versus controls, respectively) or the angiogenic response (1.1-fold of controls in liposomes alone; 1.0-fold of controls in peptides alone; p > 0.05 versus controls, respectively). Intra-muscular injection induced similar liposomal treatment effects on ischemic limb perfusion (230% of baseline) as those by intra-arterial infusion (210% of baseline; p < 0.05 versus intra-muscular).
  
  
  CONCLUSIONS
  PEGylated liposomes loaded with angiogenic peptides improved ischemic limb perfusion and promoted angiogenic responses. Liposomal angiogenic treatment via intra-arterial infusion resulted in an equally effective therapeutic efficacy compared to that of intra-muscular injection. These results show the therapeutic potential of our liposomal strategy for treating peripheral limb ischemia.
authors: a Department of Nuclear Medicine , Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital , Jeonju , South Korea.
authors: Hyosook
authors: H
authors: Hwang
authors: a Department of Nuclear Medicine , Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital , Jeonju , South Korea.
authors: Hyeon-Soo
authors: HS
authors: Kim
authors: a Department of Nuclear Medicine , Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital , Jeonju , South Korea.
authors: Hwan-Seok
authors: HS
authors: Jeong
authors: a Department of Nuclear Medicine , Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital , Jeonju , South Korea.
authors: Bagalkot Tarique
authors: BT
authors: Rajasaheb
authors: a Department of Nuclear Medicine , Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital , Jeonju , South Korea.
authors: Minjoo
authors: M
authors: Kim
authors: a Department of Nuclear Medicine , Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital , Jeonju , South Korea.
authors: Phil-Sun
authors: PS
authors: Oh
authors: a Department of Nuclear Medicine , Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital , Jeonju , South Korea.
authors: Seok Tae
authors: ST
authors: Lim
authors: a Department of Nuclear Medicine , Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital , Jeonju , South Korea.
authors: Myung-Hee
authors: MH
authors: Sohn
authors: a Department of Nuclear Medicine , Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital , Jeonju , South Korea.
authors: Hwan-Jeong
authors: HJ
authors: Jeong
mesh_terms: D042501:Angiogenic Proteins / Q000008:administration & dosage*; D000818:Animals; D002460:Cell Line; D004333:Drug Administration Routes; D005121:Extremities; D005263:Femoral Artery / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007511:Ischemia / Q000188:drug therapy*; D008081:Liposomes / Q000008:administration & dosage*; D008297:Male; D010477:Perfusion / Q000379:methods; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013667:Technetium / Q000008:administration & dosage
chemical_list: D042501:Angiogenic Proteins; D008081:Liposomes; D011092:Polyethylene Glycols; D013667:Technetium
keywords: Liposomes; ischemia; nanoparticles; peptides; therapy