Impact of Lipid/Magnesium Hydroxide Hybrid Nanoparticles on the Stability of Vascular Endothelial Growth Factor-Loaded PLGA Microspheres

Abstract

The purpose of the present study is to characterize poly(D,L-lactide-co-glycolide) (PLGA) composite microcarriers for vascular endothelial growth factor (VEGF) delivery. To reduce the initial burst release and protect the bioactivity, VEGF is encapsulated in soybean L-α-phosphatidylethanolamine (PE) and L-α-phosphatidylcholine (PC) anhydrous reverse micelle (VEGF-RM) nanoparticles. Also, mesoporous nano-hexagonal Mg(OH) 2 nanostructure (MNS)-loaded PE/PC anhydrous reverse micelle (MNS-RM) nanoparticles are synthesized to suppress the induced inflammation of PLGA acidic byproducts and regulate the release profile. The flow-focusing microfluidic geometry platforms are used to fabricate different combinations of PLGA composite microspheres (PLGA-CMPs) with MNSs, MNS-RM, VEGF-RM, and native VEGF. The essential parameters of each formulation, such as release profiles, encapsulation efficacy, bioactivity, inflammatory response, and cytotoxicity, are investigated by in vitro and in vivo studies. The results indicate that generated acidic byproducts during the hydrolytic degradation process of PLGA can be buffered, and pH values inside and outside microspheres can remain steady during degradation by MNSs. Furthermore, the significant improvement in the stability of the encapsulated VEGF is confirmed by the bioactivity assay. In vitro release study shows that the VEGF initial burst release is well minimized in the present microcarriers. The present monodisperse PLGA-CMPs can be widely used in various tissue engineering and therapeutic applications.

Tailoring biomaterials for biomimetic organs-on-chips

“…Omidi et al proposed a facile strategy to improve the biosafety and drug delivery stability of PLGA microspheres by integrating magnesium hydroxide to buffer acidic byproducts of PLGA degradation. 88 Considering the hydrophobicity of PLGA, magnesium hydroxide and therapeutic VEGF were encapsulated in anhydrous reverse micelle to improve the loading and releasing efficiency. The results revealed that the magnesium hydroxide component helped in suppressing the induced inflammation of PLGA byproducts, while the encapsulated VEGF could reach an ideal release profile.…”

Nanotechnology translation in vascular diseases: From design to the bench

“…PLGA composite microcarriers with VEGF can reduce the VEGF initial burst release and protect the bioactivity, which can suppress the induced inflammation of PLGA acidic byproducts. During the buffered hydrolytic degradation process of PLGA, the acidic byproducts can be effectively buffered, and the pH values inside and outside microspheres remain steady (Omidi et al, 2021). A dextran/PLGA‐combined microsphere system was reported to detect the release of VEGF‐A and its biological activity, which then promoted endothelial cell proliferation and capillary formation in vivo and may be a promising vector for the therapeutic vascularization of angiogenic factors (Zhang et al, 2019).…”

Fabricating Multiphasic Angiogenic Scaffolds Using Amyloid/Roxadustat-Assisted High-Temperature Protein Printing

“…As to the natural alternatives, the use of growth factors like vascular endothelial growth factor (VEGF) poses challenges due to their physicochemical instability, short half-life, high risk of improper release, and cancerous cell differentiation . Over the past decade, our group extensively explored different proangiogenics for inducing prevascularization, detailed in several papers. ,,− While previous agents have exhibited increased angiogenesis, in this study, FG-4592 (roxadustat) will be used for promoting angiogenesis. In the present study, we found that without toxicity, FG-4592 in cocultured environments with human umbilical vein endothelial cells (HUVECs)/periodontal ligament fibroblasts (PDLFs) showed a synergistic activation of angiogenesis through an intracellular mechanism.…”