Nanoparticle-encapsulated baicalein markedly modulates pro-inflammatory response in gingival epithelial cells.

Severe gum disease (periodontitis), which is one of the major global oral diseases, results from microbe-host dysbiosis and dysregulated immuno-inflammatory responses. It seriously affects oral health and general wellbeing with significant socio-economic implications. It has been well documented that natural flavonoids such as baicalin (BA) and baicalein (BE) possess potent anti-inflammatory effects. However, their intrinsic poor solubility and low bioavailability severely limit their biomedical applications. In the present study, BA and BE were encapsulated in our synthesized and amine-modified mesoporous silica nanoparticles (MSNs) (Nano-BA and Nano-BE, respectively), and their loading efficiencies and releasing profiles were investigated. Their cytotoxicity was examined on primary human gingival epithelial cells (hGECs), and the cellular uptake of Nano-BA or Nano-BE was visualized via a transmission electron microscope. Their anti-inflammatory effects were evaluated in IL-1ß-treated hGECs using the cytokine array and enzyme-linked immunosorbent assay. The present study shows that the amine-modified MSNs could encapsulate BA and BE, and nano-encapsulation greatly enhances the drug delivery rate and prolongs the release of BA and BE up to 216 h. Moreover, both Nano-BA and Nano-BE could be internalized by hGECs and retained intracellularly in nanoparticle-free media for at least 24 h. Note that Nano-BE pre-treatment effectively down-regulates the IL-1ß-induced expression of IL-6 and IL-8 in hGECs. In conclusion, nanoparticle-encapsulated BE exhibits notable anti-inflammatory effects through effective release and cellular internalization approaches. This study may facilitate the development of novel drug delivery systems for improving oral care.

The spherical nanoparticle-encapsulated chlorhexidine enhances anti-biofilm efficiency through an effective releasing mode and close microbial interactions.

We reported two forms (sphere and wire) of newly fabricated chlorhexidine (CHX)-loaded mesoporous silica nanoparticles (MSNs), and investigated their releasing capacities and anti-biofilm efficiencies. The interactions of the blank MSNs with planktonic oral microorganisms were assessed by field emission scanning electron microscopy. The anti-biofilm effects of the two forms of nanoparticle-encapsulated CHX were examined by 2,3-bis (2-methoxy- 4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide. The profiles of biofilm penetration were analyzed by fluorescent-labeled MSNs using confocal microscopy and ImageJ. The spherical MSNs with an average diameter of 265 nm exhibited a larger surface area and faster CHX-releasing rate than the MSN wires. The field emission scanning electron microscopy images showed that both shaped MSNs enabled to attach and further fuse with the surfaces of testing microbes. Meanwhile, the nanoparticle-encapsulated CHX could enhance the anti-biofilm efficiency with reference to its free form. Notably, the spherical nanoparticle-encapsulated CHX presented with a greater anti-biofilm capacity than the wire nanoparticle-encapsulated CHX, partly due to their difference in physical property. Furthermore, the relatively even distribution and homogeneous dispersion of spherical MSNs observed in confocal images may account for the enhanced penetration of spherical nanoparticle-encapsulated CHX into the microbial biofilms and resultant anti-biofilm effects. These findings reveal that the spherical nanoparticle-encapsulated CHX could preferably enhance its anti-biofilm efficiency through an effective releasing mode and close interactions with microbes.

Cellular Interactions and Formation of an Epithelial "Nanocoating-Like Barrier" with Mesoporous Silica Nanoparticles.

Oral mucosa as the front-line barrier in the mouth is constantly exposed to a complex microenvironment with multitudinous microbes. In this study, the interactions of mesoporous silica nanoparticles (MSNs) with primary human gingival epithelial cells were analyzed for up to 72 h, and their diffusion capacity in the reconstructed human gingival epithelia (RHGE) and porcine ear skin models was further assessed at 24 h. It was found that the synthesized fluorescent mesoporous silica nanoparticles (RITC-NPs) with low cytotoxicity could be uptaken, degraded, and/or excreted by the human gingival epithelial cells. Moreover, the RITC-NPs penetrated into the stratum corneum of RHGE in a time-dependent manner, while they were unable to get across the barrier of stratum corneum in the porcine ear skins. Consequently, the penetration and accumulation of RITC-NPs at the corneum layers of epithelia could form a "nanocoating-like barrier". This preliminary proof-of-concept study suggests the feasibility of developing nanoparticle-based antimicrobial and anti-inflammatory agents through topical application for oral healthcare.