Remodeling immune microenvironment in periodontitis using resveratrol liposomes as an antibiotic-free therapeutic strategy

Abstract

Background Periodontitis is a complicated inflammatory disease that damages the tooth-supporting tissues, with limited pharmacotherapy available. Macrophage-targeting therapy is promising for inflammatory diseases. Resveratrol (RSV), a nonflavonoid polyphenol, is known for its anti-inflammatory and immunomodulatory effects. However, its medical application is limited by its poor stability and water-solubility, as well as its low bioavailability. Result A therapeutic resveratrol-loaded liposomal system (Lipo-RSV) was developed to treat periodontitis. The physical properties of Lipo-RSV and its ability to regulate macrophages were investigated. The results showed that Lipo-RSV had good biocompatibility and could re-educate the inflammatory macrophages from M1- to M2-like phenotype through activating p-STAT3 and downregulating p-STAT1. Besides, the Lipo-RSV could scavenge ROS and inhibit the NF-κB signal and inflammasomes, thereby reducing the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Conclusion These results revealed that Lipo-RSV could be a potential therapeutic system for the antibiotic-free treatment for periodontal diseases. Graphical Abstract

Lipid nanoparticle-based formulations for high-performance dentistry applications

“…229,[240][241][242][243] Liposome formulations were programmed to release the payload by external stimuli as sound waves or alter the immune microenvironment for the betterment of the inflamed tissue. 239,[244][245][246] In addition, to take advantage of naturally occurring carotenoid molecules such as lycopene that can have a counteracting deleterious effect on oxidative stress, the molecular delivery using lipid NPs was explored in a human clinical study. The study concluded a protective effect and reduced oxidative damage to proteins in the compromised periodontium tissue.…”

Lipocalin 2, synthesized using a cell‐free protein synthesis system and encapsulated into liposomes, inhibits the adhesion of Porphyromonas gingivalis to human oral epithelial cells

“…Antibacterial and anti-inflammatory medications such as minocycline, doxycycline, metronidazole, and chlorhexidine were included in carrier devices and transported to periodontal pockets and 33,[58][59][60] On the other hand, some gels/pastes, fibers, strips, capsules, particles, and liposomes are known as DDS devices, 33 and several carrier devices are used for periodontal treatments. 59,60 Shi et al 61 showed that resveratrol encapsulated in liposomes ameliorated an experimental periodontitis in mice. When A. actinomycetemcomitans-infected human oral keratinocytes were cultured with liposomes that had their surfaces grafted with cyclodextrin, a cytotoxicity of keratinocytes and nitric oxide production were decreased significantly.…”

Recent progress in nanotechnology-based drug carriers for resveratrol delivery

“…However, conventional liposomes are unstable during storage (Caddeo et al., 2018 ) and have low targeting ability (Laginha et al., 2005 ). Therefore, RES-loaded liposomes were modified with poly(ethylene glycol) (PEG), resulting in a nanoplatform (PEG-lip-RES) with better stability and biocompatibility; low toxicity against murine macrophage cells (RAW264.7), mouse fibroblast cells (L929), and human vascular endothelial cells (HUVEC); prolonged half-life; and good anti-oxidant effects (Shi et al., 2021 ). In another study, the surface of liposomes was modified with chitosan and then coated with gold nanoshells to construct multifunctional liposomes responsive to pH and near-infrared light that released RES in a controlled manner, leading to synergistic antitumor effects against HeLa cells (Wang et al., 2017 ).…”