title: In vitro studies and modeling of a controlled-release device for root canal therapy.
abstract: Endodontic disease is caused primarily by bacteria that interact with periradicular host tissues. Therefore, treatment of endodontic disease aims at the exclusion of bacteria from the root canal system. This work focused on in vitro studies and modeling of a controlled-release device for delivering antimicrobial agents in root canals. A cylindrical, needle-shaped device was prepared consisting of a matrix core and a polymer coating, loaded with 30-45% chlorhexidine (CHX). The composition of the core, a blend of water-permeable polymers, and the thickness of the coating were tailored to impart various release rates. A relatively steady release rate for over 40 days after an initial burst was achieved using a formulation for long-term release, which is desirable for establishing and maintaining the necessary therapeutic levels. Mathematical models were developed for both in vitro and in vivo drug release into a liquid of limited volume, taking into account a moving boundary of the dispersed drug and a time-dependent boundary condition. A concentration-dependent effective diffusion coefficient was used to count increased porosity as the solid drug had dissolved. The finite element method and computer programs were applied to solve the differential equations and predict the in vitro and in vivo release kinetics. The model prediction agreed well with the in vitro experimental data and provided guidance for designing the device for in vivo release in root canals. The result of in vitro antimicrobial tests, performed using a bovine tooth model, suggested that the device was effective in reducing growth of microbes.
authors.affiliation: Faculty of Pharmacy, University of Toronto, M5S 2S2, Toronto, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.forename: H L
authors.initials: HL
authors.lastname: Wong
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: X Y
authors.initials: XY
authors.lastname: Wu
authors.forename: H
authors.initials: H
authors.lastname: Grad
authors.forename: R
authors.initials: R
authors.lastname: Komorowski
authors.forename: S
authors.initials: S
authors.lastname: Friedman
mesh_terms: D000465:Algorithms; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage*; D001419:Bacteria / Q000187:drug effects; D002710:Chlorhexidine / Q000008:administration & dosage / Q000493:pharmacokinetics; D003198:Computer Simulation; D003692:Delayed-Action Preparations; D003786:Dental Pulp Cavity / Q000382:microbiology*; D013293:Enterococcus faecalis / Q000187:drug effects; D007700:Kinetics; D008954:Models, Biological; D010539:Permeability; D012388:Root Canal Irrigants / Q000008:administration & dosage*; D012995:Solubility; D007507:Therapeutic Irrigation
chemical_list: D000891:Anti-Infective Agents, Local; D003692:Delayed-Action Preparations; D012388:Root Canal Irrigants; D002710:Chlorhexidine