Hyaluronic acid/Chitosan nanoparticles as delivery vehicles for VEGF and PDGF-BB.
The development of a vascular network in tissue-engineered constructs is a fundamental bottleneck of bioregenerative medicine, particularly when the size of the implant exceeds a certain limit given by diffusion lengths and/or if the host tissue shows a very active metabolism. One of the approaches to achieve the vascularization of tissue constructs is generating a sustained release of proangiogenic factors from the ischemic site. This work describes the formation and characterization of hyaluronic acid-chitosan (HA/CS) nanoparticles for the delivery of two pro-angiogenic growth factors: vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF-BB). These nanoparticles were prepared by an ionic gelification technique, and different formulations were developed by encapsulating the growth factors in association with two stabilizing agents: bovine serum albumin or heparin sodium salt. These carriers were characterized with regard to their physicochemical properties, their stability in biological media, and their cytotoxicity in the C3a hepatoma cell line. The results show that nanoparticles around 200 nm can be prepared by this method. HA/CS nanoparticles were stable when incubated in EMEM cell culture medium or in water at 37°C for 24 h. Cell culture tests confirmed that HA/CS nanoparticles are not cytotoxic within the concentration range used for growth factor delivery. Moreover, HA/CS nanoparticles were able to entrap efficiently both growth factors, reaching association values of 94% and 54% for VEGF and PDGF, respectively. In vitro release studies confirm that PDGF-BB is released from HA/CS nanoparticles in a sustained manner over approximately 1 week. On the other hand, VEGF is completely released within the first 24 h.
Parajó
Yolanda
Y
Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, Spain.
D'Angelo
Ivana
I
Welle
Alexander
A
Garcia-Fuentes
Marcos
M
Alonso
María José
MJ
D000818:Animals; D000077214:Becaplermin; D001672:Biocompatible Materials / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular; D002417:Cattle; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005079:Excipients; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D007511:Ischemia / Q000188:drug therapy / Q000209:etiology; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000493:pharmacokinetics / Q000627:therapeutic use; D020574:Proto-Oncogene Proteins c-sis; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D023822:Tissue Engineering; D019737:Transplants / Q000009:adverse effects; D042461:Vascular Endothelial Growth Factor A / Q000493:pharmacokinetics / Q000627:therapeutic use
D001672:Biocompatible Materials; D004337:Drug Carriers; D005079:Excipients; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A; D000077214:Becaplermin; D012710:Serum Albumin, Bovine; D006820:Hyaluronic Acid; D006493:Heparin; D048271:Chitosan