Proanthocyanidins-Loaded Nanoparticles Enhance Dentin Degradation Resistance.

Previous studies reported that grapeseed extract (GSE), which is rich in proanthocyanidins (PAs), improves the biodegradation resistance of demineralized dentin. This study aimed to investigate the effect of a new GSE delivery strategy to demineralized dentin through loading into biodegradable polymer poly-[lactic-co-glycolic acid] (PLGA) nanoparticles on the biodegradation resistance in terms of structural stability and surface/bulk mechanical and biochemical properties with storage time in collagenase-containing solutions. GSE-loaded nanoparticles were synthetized by nanoprecipitation at PLGA/GSE (w/w) ratios of 100:75, 100:50, and 100:25 and characterized for their morphological/structural features, physicochemical characteristics, and drug loading, entrapment, and release. Nanoparticle suspensions in distilled water (12.5% w/v) were applied (1 min) to demineralized dentin specimens by simulating pulpal pressure. The nanoparticle delivery was investigated by scanning electron microscopy (SEM)/transmission electron microscopy (TEM), and the GSE release from the delivered nanoparticles was further characterized. The variations in surface and bulk mechanical properties were characterized in terms of reduced elastic-modulus, hardness, nanoindentation testing, and apparent elastic-modulus with a storage time up to 3 mo. Hydroxyproline release with exposure to collagenase up to 7 d was estimated. An etch-and-rinse dentin adhesive was applied to investigate the morphology of the resin-dentin interface after nanoparticle delivery. Treatment with the GSE-loaded nanoparticles enhanced the collagen fibril structural resistance, reflected from the TEM investigation, and improved the biomechanical and biochemical stability of demineralized dentin. Nanoparticles having PLGA/GSE of 100:75 (w/w) showed the highest cumulative GSE release and were associated with the best improvement in biodegradation resistance. TEM/SEM showed the ability of the nanoparticles to infiltrate dentinal tubules' main and lateral branches. SEM revealed the formation of a uniform hybrid layer and well-formed resin tags with the presence of numerous nanoparticles located within the dentinal tubules and/or attached to the resin tag. This study demonstrated the potential significance of delivering collagen crosslinkers loaded into biodegradable polymer nanoparticles through the dentinal tubules of demineralized dentin on the biodegradation resistance.

Chlorhexidine Nanocapsule Drug Delivery Approach to the Resin-Dentin Interface.

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.