title: In vivo administration of VEGF- and GDNF-releasing biodegradable polymeric microspheres in a severe lesion model of Parkinson's disease.
abstract: In this work, the neuroregenerative potentials of microencapsulated VEGF, GDNF and their combination on a severely lesioned rat model were compared with the aim of developing a new strategy to treat advanced stages of Parkinson's disease. Both neurotrophic factors were separately encapsulated into polymeric microspheres (MSs) to obtain a continuous drug release over time. The regenerative effects of these growth factors were evaluated using a rotation behaviour test and quantified by the number of surviving TH+cells. The biological activities of encapsulated vascular endothelial growth factor (VEGF) and glial cell line-derived neurotrophic factor (GDNF) were investigated in HUVEC and PC12 cells, respectively. The treatment of 6-OHDA-lesioned rats with GDNF microspheres and with both VEGF and GDNF microspheres resulted in improved results in the rotation behaviour test. Both groups also showed higher levels of neuroregeneration/neuroreparation in the substantia nigra than the control group did. These results were confirmed by the pronounced TH+neuron recovery in the group receiving VEGF+GDNF-MS, demonstrating regenerative effects.
authors: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria, Spain.
authors: Enara
authors: E
authors: Herrán
authors: José Ángel
authors: JÁ
authors: Ruiz-Ortega
authors: Asier
authors: A
authors: Aristieta
authors: Manoli
authors: M
authors: Igartua
authors: Catalina
authors: C
authors: Requejo
authors: José Vicente
authors: JV
authors: Lafuente
authors: Luisa
authors: L
authors: Ugedo
authors: José Luis
authors: JL
authors: Pedraz
authors: Rosa María
authors: RM
authors: Hernández
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008863:Microspheres; D009416:Nerve Regeneration; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D010300:Parkinson Disease / Q000188:drug therapy*; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D012038:Regeneration; D013378:Substantia Nigra / Q000187:drug effects; D013499:Surface Properties; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D011108:Polymers; D042461:Vascular Endothelial Growth Factor A
keywords: 6-OHDA; GDNF; Growth factors; Microparticles; PLGA; Parkinson’s disease; VEGF