Physical key properties of antibiotic-free, PLGA/HPMC-based in-situ forming implants for local periodontitis treatment

Abstract

In-situ forming implants (ISFI) offer an interesting potential for the treatment of periodontitis, allowing for time-controlled drug release directly at the site of action (which is difficult to reach). For this purpose, ISFI loaded with antibiotics have been reported in the literature. But the use of antibiotic drugs at low doses over prolonged periods of time can lead to the development of bacterial resistances. This risk should be avoided. The aim of this study was to develop a novel type of in-situ forming implants, loaded with the antiseptic drug chlorhexidine. Special emphasis was placed on the physical properties of the systems, assuring a reliable residence time in the periodontal pockets of patients suffering from periodontitis. In particular, the risk of premature, accidental loss of the formulations due to mechanical stress (e.g. during tooth brushing and chewing) was to be reduced. Two commercially available drug products for local periodontitis treatment were studied for reasons of comparison: Chlo-site and Parocline. The syringeability and swelling behavior of the formulations were investigated, and the hardness, springiness, resilience and “stickiness” of the systems determined using extracted human teeth. Interestingly, the novel in-situ forming implants, based on PLGA/HPMC and being free of antibiotics, exhibit highly promising physical key properties: They are intensively sticking to teeth’ surfaces and provide adequate mechanical strength to assure reliable and prolonged residence times in periodontal pockets. In contrast, the commercial drug products showed limited adhesion and either rapidly shrank (Chlo-site), or substantially swelled and were mechanically very weak (Parocline).