Anti-inflammatory Periodontal Therapy with Smart Drug-Delivery-Systems (PERIO- SmaDDS)

• Applicants: Professorin Dr. Kerstin Danker; Professor Dr. Henrik Dommisch; Professor Dr. Rainer Haag
• Subject Area: Dentistry, Oral Surgery
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 417829801

Periodontitis is a widespread disease that affects approximately half of the world's population to varying degrees. The problem is not only the degradation of the periodontium caused by chronic inflammation, but also the increased risk of cardiovascular, cerebrovascular and neurodegenerative diseases. If left untreated, periodontitis not only leads to tooth loss, but also has significant negative systemic effects on the patient's overall health. To date, there is no satisfactory therapeutic option to address the inflammatory component during periodontitis. While systemic anti-inflammatory therapies have a high side effect profile, topical therapy in the oral cavity is limited by several factors such as saliva and the crevicular fluid, which reduce the bioavailability. To improve the bioavailability of active compounds on the oral mucosa, nanocarrier systems (NC) were developed in the last funding period with the aim of achieving high mucosal adhesion to increase the penetration of the NC into the mucosa and thus a high release of the drugs. Two NCs demonstrated superior properties: 1. dPGS-PCL97, a biodegradable polymer that has an intrinsic anti-inflammatory profile and adheres very rapidly to in vitro models of oral mucosa, even in the presence of saliva. 2. a catechol-functionalized core-multishell (CMS) NC. This modification mimics the mussel and increases adhesion to moist surfaces. CMS-NC improves the release of hydrophobic drugs such as dexamethasone (Dx) into the oral mucosa compared to conventional Dx formulations. Based on these results, the mucoadhesion of the dPGS-PCL97 polymer will be further improved by the biomimetic approach of catechol functionalization. In addition, the polymer will be further developed into a drug delivery system (DDS) optimized for the oral mucosa by supplementing the intrinsic anti-inflammatory effect with the promising drugs tofacitinib and doxycycline. The drugs will also be encapsulated in the catechol-functionalized CMS-NC. In addition to simpler in vitro models, a periodontitis mouse model will be used to test the effects of DDS. For transfer to the human situation, an immunocompetent human in vitro mucosal equivalent will be adapted and used to test the mucosa-specific DDS, which also complies with the 3R principle to reduce or avoid animal testing. The overall aim of the project is to develop a mucosa-specific, effective DDS with high mucosal adhesive and penetration properties combined with a strong anti-inflammatory effect that resolves the chronic inflammatory process of periodontitis.

• DFG Programme: Research Grants
• International Connection: France
• Cooperation Partner: Professorin Dr. Marjolaine Gosset