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Application of Lyophilized Gene-Delivery Formulations to Dental Implant Surfaces: Non-Cariogenic Lyoprotectant Preserves Transfection Activity of Polyplexes Long-Term

JOURNAL OF PHARMACEUTICAL SCIENCES(2023)

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Abstract
Titanium is the metal of choice for dental implants because of its biocompatibility and ability to merge with human bone tissue. Despite the great success rate of dental implants, early and late complications occur. Coating titanium dental implant surfaces with polyethyleneimine (PEI)-plasmid DNA (pDNA) polyplexes improve osseointegration by generating therapeutic protein expression at the implantation site. Lyophiliza-tion is an approach for stabilizing polyplexes and extending their shelf life; however, most lyoprotectants are sugars that can aid bacterial growth in the peri-implant environment. In our research, we coated titanium surfaces with polyplex solutions containing varying amounts of lyoprotectants. We used two common lyo-protectants (sucrose and polyvinylpyrrolidone K30) and showed for the first time that sucralose (a sucrose derivative used as an artificial sweetener) might act as a lyoprotectant for polyplex solutions. Human embry-onic kidney (HEK) 293T cells were used to quantify the transfection efficiency and cytotoxicity of the poly-plex/lyoprotectant formulations coating titanium surfaces. Polyplexes that were lyophilized in the presence of a lyoprotectant displayed both preserved particle size and high transfection efficiencies. Polyplexes lyophi-lized in 2% sucralose have maintained transfection efficacy for three years. These findings suggest that modi-fying dental implants with lyophilized polyplexes might improve their success rate in the clinic.(c) 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.
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Key words
Polyplexes,Gene delivery,Non -viral gene delivery,Lyophilization,Lyoprotectants,Stability,Titanium dental implants,Osseointegration
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