Nanoparticles based on PLGA:poloxamer blends for the delivery of proangiogenic growth factors.
New blood vessel formation is a critical requirement for treating many vascular and ischemia related diseases, as well as for many tissue engineering applications. Angiogenesis and vasculogenesis, in fact, represent crucial processes for the functional regeneration of complex tissues through tissue engineering strategies. Several growth factors (GFs) and signaling molecules involved in blood vessels formation have been identified, but their application to the clinical setting is still strongly limited by their extremely short half-life in the body. To overcome these limitations, we have developed a new injectable controlled release device based on polymeric nanoparticles for the delivery of two natural proangiogenic GFs: platelet derived growth factor (PDGF-BB) and fibroblast growth factor (FGF-2). The nanoparticle system was prepared by a modified solvent diffusion technique, encapsulating the GF both in presence and in the absence of two stabilizing agents: bovine serum albumin (BSA) and heparin sodium salt (Hp). The developed nanocarriers were characterized for morphology, size, encapsulation efficiency, release kinetics in vitro and GF activity in cell cultures. The results have indicated that the coencapsulation of stabilizing agents can preserve the GF active structure and, in addition, increase their encapsulation efficiency into nanoparticles. Through this optimization process, we were able to raise the encapsulation efficiency of FGF-2 to 63%, and that of PDGF-BB to 87%. These PLGA:poloxamer blend nanoparticles loaded with GFs were able to release PDGF-BB and FGF-2 in a sustained fashion for more than a month. This work also confirms other positive features of PLGA:poloxamer nanoparticles. Namely, they are able to maintain their stability in simulated biological medium, and they are also nontoxic to cell culture models. Incubation of nanoparticles loaded with FGF-2 or PDGF-BB with endothelial cell culture models has confirmed that GFs are released in a bioactive form. Altogether, these results underline the interest of PLGA:poloxamer nanoparticles for the controlled delivery of GFs and substantiate their potential for the treatment of ischemic diseases and for tissue engineering applications.
d'Angelo
Ivana
I
Department of Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Garcia-Fuentes
Marcos
M
Parajó
Yolanda
Y
Welle
Alexander
A
Vántus
Tibor
T
Horváth
Anikó
A
Bökönyi
Györgyi
G
Kéri
György
G
Alonso
Maria José
MJ
D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage*; D000818:Animals; D000077214:Becaplermin; D002417:Cattle; D016503:Drug Delivery Systems; D004355:Drug Stability; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005612:Freeze Drying; D056945:Hep G2 Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000633:toxicity; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity / Q000648:ultrastructure; D020442:Poloxamer / Q000737:chemistry / Q000633:toxicity; D011100:Polyglycolic Acid / Q000737:chemistry / Q000633:toxicity; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020574:Proto-Oncogene Proteins c-sis / Q000008:administration & dosage* / Q000493:pharmacokinetics
D043925:Angiogenesis Inducing Agents; D053769:Nanocapsules; D020574:Proto-Oncogene Proteins c-sis; D016222:Fibroblast Growth Factor 2; D020442:Poloxamer; D000077214:Becaplermin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid