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.

Effect on adhesion of a nanocapsules-loaded adhesive system

“…23,24 Incorporating NCs into the primer and adhesive did not compromise the immediate bond strength, as has been observed in previous studies, 7,9 indicating the reliable distribution of NCs in the hybrid layer. 6,9 Previous studies that tested commercial and experimental adhesives showed similar bond strength results. 25,26 Storage in water satisfactorily mimics clinical restoration degradation 23,27 since it infiltrates, promotes the swelling of and reduces the forces between polymer chains, 10 causing a decrease in the mechanical properties, the elution of monomers and a consequent weakening of the bond.…”

“…9 The chemical affinity between the polymer of the NCs and the monomers of the adhesive system leads to reliable physicochemical properties. 6,7,8,9 The diffusion of nanocapsules in the hybrid layer did not result in a decrease in the immediate bond strength. 7,9 Nonetheless, the influence of the nanocapsules on the long-term bond strength has not yet been elucidated.…”

“…3,4,5 Due to these favorable conditions, nanocapsules containing drugs have been applied in dental adhesive systems, promoting certain therapeutic effects, such as anti-inflammatory effects in the pulp tissue and antimicrobial effects to protect against caries, without compromising the physicochemical properties of the adhesive. 6,7,8 Nanocapsules applied to dentin as formulations with water, primer or adhesive promote drug diffusion up to 0.75 mm into dentin. 6,7,8 In the hybrid layer, the nanocapsules incorporated in the adhesive were seen to be dispersed over the intertubular dentin surface and penetrate into the dentinal tubules.…”

“…6,7,8 Nanocapsules applied to dentin as formulations with water, primer or adhesive promote drug diffusion up to 0.75 mm into dentin. 6,7,8 In the hybrid layer, the nanocapsules incorporated in the adhesive were seen to be dispersed over the intertubular dentin surface and penetrate into the dentinal tubules. 6,9 The well-dispersed particles and spherical shape of the NCs avoid stress concentration in the adhesive, thus improving its properties.…”

“…6,7,8 In the hybrid layer, the nanocapsules incorporated in the adhesive were seen to be dispersed over the intertubular dentin surface and penetrate into the dentinal tubules. 6,9 The well-dispersed particles and spherical shape of the NCs avoid stress concentration in the adhesive, thus improving its properties. 9 The chemical affinity between the polymer of the NCs and the monomers of the adhesive system leads to reliable physicochemical properties.…”