Neovascularization by Sustained Delivery of G-CSF, EPO and VEGF Using Dextran/PLGA Microspheres.

Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8703941 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1615-5947 (Electronic) Linking ISSN: 08905096 NLM ISO Abbreviation: Ann Vasc Surg Subsets: MEDLINE

Publication: <2007->: Netherlands : Elsevier
Original Publication: Detroit : [Published by Expansion scientifique française for Annals of Vascular Surgery, Inc. and Association pour la promotion de la chirurgie vasculaire, Paris, c1986-

Drug Carriers*; Angiogenesis Inducing Agents/*administration & dosage ; Dextrans/*chemistry ; Erythropoietin/*administration & dosage ; Granulocyte Colony-Stimulating Factor/*administration & dosage ; Ischemia/*drug therapy ; Muscle, Skeletal/*blood supply ; Neovascularization, Physiologic/*drug effects ; Polyesters/*chemistry ; Vascular Endothelial Growth Factor A/*administration & dosage; Angiogenesis Inducing Agents/chemistry ; Animals ; Cell Proliferation/drug effects ; Delayed-Action Preparations ; Disease Models, Animal ; Drug Compounding ; Drug Liberation ; Erythropoietin/chemistry ; Granulocyte Colony-Stimulating Factor/chemistry ; Hindlimb ; Injections, Intramuscular ; Ischemia/pathology ; Ischemia/physiopathology ; Kinetics ; Male ; Microspheres ; Muscle, Smooth, Vascular/drug effects ; Muscle, Smooth, Vascular/metabolism ; Muscle, Smooth, Vascular/pathology ; Myocytes, Smooth Muscle/drug effects ; Myocytes, Smooth Muscle/metabolism ; Myocytes, Smooth Muscle/pathology ; Particle Size ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A/chemistry

Background: Therapeutic neovascularization has some obstacles, such as it requires more than one proangiogenic factor, and these factors have short half-lives. To overcome these obstacles, combined delivery of granulocyte-colony stimulating factor (G-CSF), erythropoietin (EPO) and vascular endothelial growth factor (VEGF) using protein/dextran/poly (lactic-co-glycolic acid) (PLGA) sustained-release microspheres was proposed to promote neovascularization.
Methods: Dextran microparticles loaded with G-CSF, EPO or VEGF were prepared and encapsulated in PLGA microspheres to obtain protein-dextran-PLGA microspheres. The release behavior of microspheres was studied in vitro. The protein/dextran/PLGA microspheres were injected into the ischemic hindlimbs of rats. Neovascularization in ischemic muscle was measured.
Results: Microspheres released G-CSF, EPO and VEGF in vitro for more than 4 weeks. Combined therapy with VEGF, EPO and G-CSF promoted the expression of B-cell lymphoma-2 and stromal cell-derived factor 1, cellular proliferation and the incorporation of C-X-C chemokine receptor 4 positive cells. Capillary density and smooth muscle α-actin+ vessel density were higher in the combined treatment of VEGF, EPO and G-CSF than in the single factor treatment.
Conclusions: The combined and sustained delivery of VEGF, EPO and G-CSF using dextran-PLGA microspheres had a more significant neovascularization effect than monotherapy with each factor alone. This combined therapy might be a promising treatment for ischemic vascular diseases.
(Copyright © 2019 Elsevier Inc. All rights reserved.)

0 (Angiogenesis Inducing Agents)
0 (Delayed-Action Preparations)
0 (Dextrans)
0 (Drug Carriers)
0 (EPO protein, human)
0 (Polyesters)
0 (Vascular Endothelial Growth Factor A)
0 (dextran-poly(lactide-co-glycolide))
0 (vascular endothelial growth factor A, rat)
11096-26-7 (Erythropoietin)
143011-72-7 (Granulocyte Colony-Stimulating Factor)

Date Created: 20191022 Date Completed: 20200824 Latest Revision: 20200824

20250114

10.1016/j.avsg.2019.10.033

31634610