Nanoparticular delivery system for a secretoneurin derivative induces angiogenesis in a hind limb ischemia model

• Published in: Journal of controlled release Vol. 250; pp. 1 - 8
• Main Authors: Albrecht-Schgoer, Karin, Barthelmes, Jan, Schgoer, Wilfried, Theurl, Markus, Nardin, Isabelle, Lener, Daniela, Gutmann, Clemens, Dünnhaupt, Sarah, Bernkop-Schnürch, Andreas, Kirchmair, Rudolf
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 28-03-2017
• Subjects: Angiogenesis; Angiogenesis Inducing Agents - administration & dosage; Angiogenesis Inducing Agents - chemistry; Angiogenesis Inducing Agents - pharmacology; Animals; Apoptosis - drug effects; Bioactivity; Cell Proliferation - drug effects; Chitosan; Chitosan - chemistry; Chromatography, High Pressure Liquid; Drug Delivery Systems; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Hindlimb - blood supply; Hindlimb - drug effects; Human Umbilical Vein Endothelial Cells - cytology; Human Umbilical Vein Endothelial Cells - drug effects; Humans; Ischemia - drug therapy; Ischemia - physiopathology; Mice; Muscle, Skeletal - blood supply; Muscle, Skeletal - drug effects; Nanoparticle; Nanoparticles - chemistry; Neovascularization, Physiologic - drug effects; Neuropeptides - administration & dosage; Neuropeptides - chemistry; Neuropeptides - pharmacology; Particle Size; Peptide; Peripheral Arterial Disease - drug therapy; Peripheral Arterial Disease - physiopathology; Screening; Secretogranin II - administration & dosage; Secretogranin II - chemistry; Secretogranin II - pharmacology; Angiogenesis; Screening; Bioactivity; Chitosan; Nanoparticle; Peptide
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2017.02.004

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.
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