title: Chlorhexidine Nanocapsule Drug Delivery Approach to the Resin-Dentin Interface.
abstract: In this study, we are introducing a new drug-delivery approach to demineralized dentin substrates through microsized dentinal tubules in the form of drug-loaded nanocapsules. Chlorhexidine (CHX) is widely used in adhesive dentistry due to its nonspecific matrix metalloproteinase inhibitory effect and antibacterial activities. Poly(ε-caprolactone) nanocapsules (nano-PCL) loaded with CHX were fabricated by interfacial polymer deposition at PCL/CHX ratios of 125:10, 125:25, and 125:50. Unloaded nanocapsules (blank) were fabricated as control. The fabricated nanocapsules were characterized in vitro in terms of particle size, surface charges, particle recovery, encapsulation efficiency, and drug loading. Nanocapsule morphology, drug inclusion, structural properties, and crystallinity were investigated by scanning and transmission electron microscopes (SEM/TEM), energy-dispersive x-ray analysis, Fourier transform infrared spectroscopy, and x-ray diffraction. Initial screening of the antibacterial activities and the cytotoxicity of the nanocapsules were also conducted. Nanocapsules, as carried on ethanol/water solution, were delivered to demineralized dentin specimens connected to an ex vivo model setup simulating the pulpal pressure to study their infiltration, penetration depth, and retention inside the dentinal tubules by SEM/TEM. Nanocapsules were Ag labeled and delivered to demineralized dentin, followed by the application of a 2-step etch-and-rinse dentin adhesive. CHX-release profiles were characterized in vitro and ex vivo up to 25 d. Spherical nanocapsules were fabricated with a CHX core coated with a thin PCL shell. The blank nanocapsules exhibited the largest z-average diameter with negatively charged ζ-potential. With CHX incorporation, the nanocapsule size was decreased with a positive shift in ζ-potential. Nano-PCL/CHX at 125:50 showed the highest drug loading, antibacterial effect, and CHX release both in vitro and ex vivo. SEM and TEM revealed the deep penetration and retention of the CHX-loaded nanocapsules inside dentinal tubules and their ability to be gradually degraded to release CHX in vitro and ex vivo. Ag-labeled nanocapsules revealed the close association and even distribution of nanocapsules throughout the resin tag structure. This study demonstrated the potential of introducing this novel drug-delivery approach to demineralized dentin substrates and the resin-dentin interface with nanosized CHX-loaded nanocapsules through the microsized dentinal tubules.
authors.affiliation: Discipline of Oral Sciences, Faculty of Dentistry, National University of Singapore, Singapore.
authors.forename: B M
authors.initials: BM
authors.lastname: Priyadarshini
authors.affiliation: Institute of Materials Research and Engineering, Innovis, Singapore.
authors.forename: S T
authors.initials: ST
authors.lastname: Selvan
authors.affiliation: Electron Microscopy Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: T B
authors.initials: TB
authors.lastname: Lu
authors.affiliation: Discipline of Oral Sciences, Faculty of Dentistry, National University of Singapore, Singapore.
authors.forename: H
authors.initials: H
authors.lastname: Xie
authors.affiliation: Discipline of Prosthodontics, Operative Dentistry and Endodontics, Faculty of Dentistry, National University of Singapore, Singapore.
authors.forename: J
authors.initials: J
authors.lastname: Neo
authors.affiliation: Discipline of Oral Sciences, Faculty of Dentistry, National University of Singapore, Singapore denasfmf@nus.edu.sg.
authors.forename: A S
authors.initials: AS
authors.lastname: Fawzy
mesh_terms: D000891:Anti-Infective Agents, Local / Q000008:administration & dosage* / Q000627:therapeutic use; D002710:Chlorhexidine / Q000008:administration & dosage* / Q000627:therapeutic use; D003188:Composite Resins / Q000378:metabolism*; D003804:Dentin / Q000187:drug effects / Q000378:metabolism*; D017220:Dentin-Bonding Agents / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D053769:Nanocapsules / Q000008:administration & dosage*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000891:Anti-Infective Agents, Local; D003188:Composite Resins; D017220:Dentin-Bonding Agents; D053769:Nanocapsules; D002710:Chlorhexidine
keywords: antibacterial agents; biodegradation; collagen; dentin-bonding agents; dentinal fluid; nanotechnology