Optimizing overnight oral appliance for sustained-release varnish delivery system of sirolimus

Abstract

<h3>Objectives</h3> Intraoral trays can be used to deliver treatment materials and medications for dental or mucosal conditions. Maintaining appropriate salivary levels of the active ingredient is challenging when using local application. We have previously analyzed salivary levels and local effects of slow-release varnishes (with clotrimazole or sirolimus as the active ingredient) during the daytime. The aims of the present study were as follows: (1) to optimize overnight appliances for slow-release medications by measuring saliva and blood levels and (2) to evaluate the safety of overnight use. <h3>Methods</h3> An acrylic tray containing 0.5 mg of sirolimus in a sustained-release varnish was applied to 6 anterior teeth for 12 hours in 10 healthy volunteers. Whole unstimulated saliva was collected 1, 2, 10, and 12 hours after application, and a blood sample was taken after 12 hours. Drug levels were analyzed. Results from slow- and fast-release formulations, varnish application position on the tray (buccal, palatal, or lingual), and tray placement (mandibular vs maxillary) were compared. The volunteers evaluated the varnish and tray. The study was approved the hospital ethics committee. <h3>Results</h3> Salivary sirolimus was undetected with use of the slow formulation. The faster formulation produced salivary concentrations of 0.3-45 ng/mL. The highest salivary levels were observed with a mandibular tray with lingual varnish application (up to 178 ng/mL). The sialometry of all participants was within normal range (0.2-2 mL/min), and the highest drug levels were found when salivary flow was lowest. The medication was undetected in the blood. No local reactions or side effects were reported. <h3>Conclusions</h3> Salivary concentrations of medications delivered using an oral tray can be affected by the release rate of formulation and, more important, by the position of the tray and the varnish within it and salivary flow rate. Overnight oral trays can be used to deliver medications especially when 24-hour drug exposure is desired. Further studies regarding local factors affecting drug release and salivary levels are required.