Nanoparticular delivery system for a secretoneurin derivative induces angiogenesis in a hind limb ischemia model.
Common therapeutic strategies for peripheral arterial disease often fail to re-establish sufficient blood flow within legs and feet of patients for avoiding critical limb ischemia, what is characterized by a substantial risk for amputation. The neuropeptide secretoneurin induces angiogenesis in models of limb and myocardial ischemia and might be a promising tool in the treatment of patients without the option of revascularization therapy for severe ischemia. Within this manuscript, the biologically active part of secretoneurin was identified, modified by induction of a cysteine residue to gain higher stability against enzymatic degradation and further packed into S-protected thiolated chitosan nanoparticles, which enable intra-muscular application of secretoneurin. Secretoneurin nanoparticles restored blood flow in a mouse hind limb ischemia model within one week, whereas control particles did not. In vitro testing also revealed the angiogenic, antiapoptotic and proliferative effects of the new secretoneurin derivate, as tested in primary human umbilical vein endothelial cells. With the work from this study we provide a new promising tool for treatment of peripheral arterial disease.
Department for Pharmacology and Genetics, Medical University Innsbruck, Innsbruck, Austria. Electronic address: Karin.Albrecht@i-med.ac.at.
Karin
K
Albrecht-Schgoer
Department of Pharmaceutical Technology, University Innsbruck, Innsbruck, Austria.
Jan
J
Barthelmes
Department of Internal Medicine III, Medical University Innsbruck, Innsbruck, Austria.
Wilfried
W
Schgoer
Department of Internal Medicine III, Medical University Innsbruck, Innsbruck, Austria.
Markus
M
Theurl
ThioMatrix GmbH, Research Center Innsbruck, Trientlgasse 65, Innsbruck, Austria.
Isabelle
I
Nardin
Department of Internal Medicine III, Medical University Innsbruck, Innsbruck, Austria.
Daniela
D
Lener
Department of Internal Medicine III, Medical University Innsbruck, Innsbruck, Austria.
Clemens
C
Gutmann
ThioMatrix GmbH, Research Center Innsbruck, Trientlgasse 65, Innsbruck, Austria.
Sarah
S
Dünnhaupt
Department of Pharmaceutical Technology, University Innsbruck, Innsbruck, Austria.
Andreas
A
Bernkop-Schnürch
Department of Internal Medicine III, Medical University Innsbruck, Innsbruck, Austria.
Rudolf
R
Kirchmair
D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007511:Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D051379:Mice; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009479:Neuropeptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size; D058729:Peripheral Arterial Disease / Q000188:drug therapy* / Q000503:physiopathology; D053381:Secretogranin II / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
D043925:Angiogenesis Inducing Agents; D009479:Neuropeptides; D053381:Secretogranin II; C081159:secretoneurin; D048271:Chitosan
Angiogenesis; Bioactivity; Chitosan; Nanoparticle; Peptide; Screening