Integration of Lipid-Functionalized Epigallocatechin-3-gallate into PLGA Matrix as a Novel Polyphenol-Based Nanoantioxidant

Cristina Minnelli; Pierluigi Stipa; Giovanna Mobbili; Simona Sabbatini; Brenda Romaldi; Tatiana Armeni; Emiliano Laudadio

doi:10.1021/acsomega.3c07637

Integration of Lipid-Functionalized Epigallocatechin-3-gallate into PLGA Matrix as a Novel Polyphenol-Based Nanoantioxidant

ACS Omega. 2023 Dec 7;8(50):48292-48303. doi: 10.1021/acsomega.3c07637. eCollection 2023 Dec 19.

Authors

Cristina Minnelli¹, Pierluigi Stipa², Giovanna Mobbili¹, Simona Sabbatini², Brenda Romaldi³, Tatiana Armeni³, Emiliano Laudadio²

Affiliations

¹ Department of Life and Environmental Science, Polytechnic University of Marche, 60121 Ancona, Italy.
² Department of Science and Engineering of Matter, Environment and Urban Planning, Polytechnic University of Marche, 60121 Ancona, Italy.
³ Department of Clinical Sciences, Polytechnic University of Marche, 60121 Ancona, Italy.

Abstract

The search for polyphenol-based materials with antioxidant activity is a growing research area in the biomedical field. To obtain an efficient and stable nanoantioxidant, a novel biosystem was designed by integrating a lipophilic derivative of epigallocatechin-3-gallate (named EGCG-C18) on the surface of poly(lactic-co-glycolic acid) (PLGA). Poly(vinyl alcohol) (PVA) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG₂₀₀₀) were selected as polymeric and lipidic stabilizers, respectively, and their influence on both physical properties and the antioxidant activity of nanoantioxidant was investigated by a combined in silico and experimental approach. Full-atom molecular dynamics (MD) simulations were carried out to describe the different self-assembly processes of all components and the interactions that guided the EGCG-C18 insertion inside the PLGA matrix. Together with infrared spectroscopy results, the formation of an antioxidant lipid shell on the PLGA surface was clear. Dynamic light scattering and transmission electron microscopy showed that in the presence of DSPE-PEG₂₀₀₀, NPs were smaller than those treated with PVA. In addition, the different stabilizers used strongly influenced the ROS-scavenging ability of nanomaterials and this effect was strictly related to the molecular organization of EGCG-C18. MD showed that the apolar interaction between the alkyl chains of DSPE-PEG₂₀₀₀ and EGCG-C18 oriented the phenolic groups of the polyphenol toward the solvent, providing an ability of NP to scavenge hydroxyl radicals over to free EGCG-C18 and PLGA/PVA NPs. Finally, the ability of nanoantioxidants to protect human dermal fibroblasts from cell death induced by oxidative stress has been tested, revealing the high potential of these novel NPs as polyphenol-based materials.