Mesoporous silica nanoparticle-encapsulated antimicrobials and Chinese herbal extracts : controlling oral microbes, modulating immuno-inflammatory response & perspectives

Abstract

Mesoporous silica nanoparticles (MSNs) as promising drug vehicles have been increasingly yet broadly applied in biomedical area, owning to their excellent physicochemical property and biocompatibility. Currently, the study on MSNs in oral science remains in a preliminary stage. As effective control of plaque biofilms and anti-inflammation play key roles in periodontal treatment, MSNs may potentially serve as a novel drug delivery system for tackling oral/periodontal infection and inflammation. The present study investigated for the first time the profiles and effects of nanoparticle-encapsulated antimicrobials/Chinese herbal extracts on controlling oral microbes and modulating immuno-inflammatory response in host cells. The thesis consists of the following parts: i) MSNs with two shapes (sphere and wire) were synthesized and applied to encapsulate chlorhexidine (CHX), and the interactions of two-shaped MSNs with microorganisms and the anti-biofilm effects of nano-encapsulated CHX were studied; ii) spherical MSNs were then applied to encapsulate the different Chinese herbal water extracts or active compounds via appropriate surface modifications; iii) two featured flavoinodis derived from Scutellaria baicalensis, baicalin (BA) and baicalein (BE), were loaded in the amine-modified spherical MSNs (Nano-BA and Nano-BE). Their anti-inflammatory effects were evaluated in THP-1-derived macrophages and primary human gingival epithelial cells (hGECs); and iv) the interactions of fluorescent-labeled MSNs (RITC-NPs) with hGECs and the penetration profiles of RITC-NPs in the reconstructed human gingival epithelia (RHGE) were assessed. The spherical MSNs showed a larger surface area and released CHX more quickly than the MSN wires. The nanoparticle-encapsulation per se could enhance the anti-biofilm efficiency of CHX. Notably, the spherical nanoparticle-encapsulated CHX exhibited a greater anti-biofilm capacity than the wire ones, due to its better physical property and biofilm diffusion rate. Both water extracts and active compounds of various Chinese herbs could be encapsulated in the spherical MSNs via proper surface modifications, and some of them were to different extent released from the nanoparticles at least for 24 h. Of them, Nano-SB with acceptable loading efficiency and release rate are deemed to be applicable for further biological assessments on their anti-inflammatory effects. Based on these results, the amine-modified MSNs were thereby utilized to encapsulate BA and BE, and the nano-encapsulation greatly prolonged their release rate up to 216 h. Moreover, both Nano-BA and Nano-BE can be internalized by THP-1 cells and hGECs, and retained intracellularly in nanoparticle-free media for at least 24 h. Interestingly, pre-treatment with Nano-BE effectively down-regulated IL-1β-induced expression of IL-6 and IL-8 in hGECs. Moreover, RITC-NPs with low cytotoxicity could be internalized and excreted by hGECs. It was noteworthy that RITC-NPs enabled to penetrate into the corneum layers of RHGE in a time-dependent manner, and their accumulation at the epithelia formed a ‘nanocoating-like’ barrier. Further study would focus on exploring the relevant biological and clinical implications. The current findings show that MSNs enable to facilitate the drug release for anti-biofilm and anti-inflammatory treatments via an effective releasing mode and intimate cellular interactions. This proof-of-concept study demonstrates the potential feasibility of developing nanoparticle-based antimicrobial and anti-inflammatory agents through topical application for better oral/periodontal healthcare.