Orally Administered EC16 Nanoparticles Attenuate Periodontitis and Cross the Blood–Brain Barrier to Modulate Neuroinflammatory Responses

Periodontal disease (PD) affects a large proportion of adults and is increasingly associated with systemic inflammation and neurodegenerative risk. However, current therapies have limited efficacy in disrupting biofilms and modulating systemic responses. In this pilot study, we evaluated epigallocatechin-3-gallate-palmitate (EGCG-palmitate or EC16) nanoparticles (NPs), a lipid-soluble derivative of epigallocatechin-3-gallate (EGCG), generated using Facilitated Self-Assembling Technology (FAST), a green nanotechnology that enables spontaneous formation of stable nanoparticles without surfactants or carrier materials. We hypothesized that EC16 NPs could inhibit periodontal pathogens and modulate neuroinflammatory responses. Antimicrobial activity was assessed in vitro, and potential therapeutic effects were evaluated in a ligature + pathogen-induced mouse model of periodontitis. EC16 NPs inhibited the growth of Porphyromonas gingivalis. Oral administration of EC16 NPs (0.02% w/v equivalent to 16-20 mg/kg) significantly reduced bacterial load and decreased alveolar bone loss by approximately 50% compared with controls. Importantly, biodistribution analysis using Cy5-labeled EC16 NPs demonstrated detectable signals in mouse brain tissue following oral gavage, indicating EC16 NPs can cross the blood–brain barrier. This represents, to our knowledge, the first evidence that an orally administered EGCG derivative in nanoparticle form reaches the central nervous system and induces biological responses. In addition, EC16 NP treatment was associated with increased regulatory T cell (Treg) populations in cervical lymph nodes and reduced expression of inflammatory (IL-1β) and senescence-related markers (p16, p53) in brain tissue. These findings demonstrate that EC16 nanoparticles possess dual local and systemic activity and support further investigation of FAST-enabled nanoformulations as a novel therapeutic strategy for periodontal disease and inflammation-related brain conditions.