Bioerodible injectable poly(ortho ester) for tetracycline controlled delivery to periodontal pockets: Preliminary trial in humans

Abstract

The semisolid consistency of poly(ortho esters) (POEs) containing tetracycline free base allows direct injection in the periodontal pocket and shows sustained and almost constant in vitro release in phosphate buffer, pH 7.4 at 37°C, for up to 14 days. Total polymer degradation concomitant with drug release was obtained. Formulations containing 10% or 20% (wt/wt) tetracycline were evaluated in a panel of 12 patients suffering from severe and recurrent periodontitis. In the first trial including 6 patients, singlerooted teeth and molar teeth with furcations were treated immediately after scaling and root planing. Patients tolerated both formulations well, experienced no pain during application, and showed no signs of irritation or discomfort during the observation period. However, retention of the formulation was minimal in this first study. An improved clinical protocol followed in the second study (stopping bleeding after scaling and root planning) prolonged the retention of the formulations in the inflamed periodontal pockets. For up to 11 days, tetracycline concentrations in the gingival crevicular fluid were higher than the minimum inhibitory concentration of tetracycline against most periodontal pathogens.

Biodegradable polymers for dental tissue engineering and regeneration

“…Such systems showed sustained release in phosphate buffer, pH 7.4 at 37 °C, for up to 14 days. These POE formulations containing 10 % or 20 % (wt/wt) tetracycline were tested in a panel of 12 patients suffering from severe and recurrent periodontitis, resulting in prolonged retention in the inflamed periodontal pockets and high tetracycline concentrations in the gingival crevicular fluid [230]. Erdmann et al investigated the effects of degradable poly(anhydride ester) implants in which the polymer backbone breaks down into salicylic acid on new bone formation.…”

Formulation development of smart gel periodontal drug delivery system for local delivery of chemotherapeutic agents with application of experimental design

“…Systems for periodontal delivery of chemotherapeutic agents include dentifrices, mouth rinses, chewing gum, gels (Southard & Godowski, 1998), suspensions, irrigation solutions, fibers, films, microparticles, and slow release devices (Jones et al, 2000;Schwach-Abdellaoui et al, 2002). These drug delivery systems have some disadvantages depending upon formulation characteristics.The sub-gingival periodontal environment was not accessible to locally delivered chemotherapeutic agents in the form of toothpastes and mouthwashes, owing to their limited ability to penetrate into the sub-gingival environment.…”

Liquid, Injectable, Hydrophobic and Biodegradable Polymers as Drug Delivery Vehicles

“…For example, inclusion of trans‐ cyclohexanedimethanol, which imparts rigidity to the polymer backbone, increased the polymer glass transition temperature, whereas inclusion of longer chain alkane diols decreased the polymer glass transition temperature;16, 17 glass transition temperatures as low as −46 °C have been reported 17. Control over the molecular weight of POE IV polymers was achieved by using an excess of diol relative to the diketene acetal or through the use of a chain‐stopper monofunctional alcohol, such as, for example, 1‐decanol 17. The number‐average molecular weight for injectable purposes was maintained below 5 000 Da, and the polydispersities ranged from 1.6 to 1.9 17…”

“…Control over the molecular weight of POE IV polymers was achieved by using an excess of diol relative to the diketene acetal or through the use of a chain‐stopper monofunctional alcohol, such as, for example, 1‐decanol 17. The number‐average molecular weight for injectable purposes was maintained below 5 000 Da, and the polydispersities ranged from 1.6 to 1.9 17…”

“…Tetracycline release from this more hydrophobic polymer lasted longer (approximately 15 days), but exhibited a more sigmoidal release pattern. This formulation was tested in humans for treatment of infection in the periodontal pocket 22. Despite the formulation being apparently well tolerated by the patients, the polymer was not retained at the injection site, with only 2 out of 24 sites having the formulation present by day 11.…”