Nanoparticles Based on PLGA:Poloxamer Blends for the Delivery of Proangiogenic Growth Factors

Abstract

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.

Acoustic droplet–hydrogel composites for spatial and temporal control of growth factor delivery and scaffold stiffness

“…As a critical component of the local, cellular microenvironment, growth factors can affect the migration, survival, proliferation and differentiation of cells. In most cases, the release of growth factors, either chemically conjugated to the scaffold material [4,5] or physically contained within particulates [6–8], is a process dominated by molecular diffusion and material degradation. The ability to modulate growth factor release from these passive systems is severely limited, especially after in vivo implantation of the scaffold.…”

Tissue engineering strategies for promoting vascularized bone regeneration

“…Similarly, pore size of the particle relative to the size of the growth factor can influence release rates from these systems. For example, PDGF and FGF encapsulated within PLGA–polymer nanoparticles has been shown to enhance angiogenesis 94 .…”

Nanoscale Strategies: Treatment for Peripheral Vascular Disease and Critical Limb Ischemia

“…To date, a variety of nanomaterials have been employed to deliver growth factors to ischemic tissues, including poly(lactic- co -glycolic acid) (PLGA), 33 PLGA: poloxamer blend NPs, 34 gold NPs 35 and graphene oxide 36 (summarized in Table 1). Even without incorporation of specific antibodies or targeting molecules, it has been shown that upon intravenous injections to mouse models, NPs (<200 nm) would preferentially accumulate in ischemic limb than in healthy limb (Figure 2).…”