The natural polyphenol Resveratrol (RSV) claims numerous positive effects on health due to the well documented biological effects demonstrating its potential as a disease-preventing agent and as adjuvant for treatment of a wide variety of chronic diseases. Since several studies, both in vitro and in vivo, have highlighted the protective bone aptitude of RSV both as promoter of osteoblasts’ proliferation and antagonist of osteoclasts’ differentiation, they could be interesting in view of applications in the field of dentistry and maxillofacial surgery. This review has brought together experimental findings on the use of RSV in the regeneration of bone tissue comprising also its application associated with scaffolds and non-transfusional hemocomponents.

Teeth extractions are often followed by alveolar bone reabsorption, although an adequate level of bone is required for reliable rehabilitations by dental implants. Leukocyte and platelet-rich fibrin (L-PRF) has been widely applied in regenerative procedures and with antibiotic and antioxidant agents could play an essential role in hard and soft tissue healing. In this work, a nanocomposite (Sponge-C-MTR) consisting of a hyaluronate-based sponge loaded with metronidazole (MTR) and nanostructured lipid carriers containing curcumin (CUR-NLC) was designed to be wrapped in the L-PRF™ membrane in the post-extraction sockets and characterized. CUR-NLCs, obtained by homogenization followed by high-frequency sonication of the lipid mixture, showed loading capacity (5% w/w), drug recovery (95% w/w), spherical shape with an average particle size of 112.0 nm, and Zeta potential of −24 mV. Sponge-C-MTR was obtained by entrapping CUR-NLC in a hydrophilic matrix by a freeze-drying process, and physico-chemical and cytocompatibility properties were evaluated. Moreover, the aptitude of CUR and MTR to the penetrate and/or permeate both L-PRF™ and porcine buccal tissue was assessed, highlighting MTR penetration and CUR accumulation promoted by the system. The results positively support the action of nanocomposite in dental tissues regeneration when applied together with the L-PRF™.

Periodontitis treatment is usually focused on the reduction or eradication of periodontal pathogens using antibiotics against anaerobic bacteria, such as metronidazole (MTR). Moreover, recently the correlation between periodontal diseases and overexpression of reactive oxygen species (ROS) led to the introduction of antioxidant biomolecules in therapy. In this work, bioadhesive buccal tablets, consisting of a hydrophilic matrix loaded with metronidazole and lipophilic nanoparticles as a vehicle of curcumin, were developed. Curcumin (CUR)-loaded nanostructured lipid carriers (NLC) were prepared using glycyrrhetic acid, hexadecanol, isopropyl palmitate and Tween®80 as a surfactant. As method, homogenization followed by high-frequency sonication was used. After dialysis, CUR-NLC dispersion was evaluated in terms of drug loading (DL, 2.2% w/w) and drug recovery (DR, 88% w/w). NLC, characterized by dynamic light scattering and scanning electron microscopy (SEM), exhibited a spherical shape, an average particle size of 121.6 nm and PDI and PZ values considered optimal for a colloidal nanoparticle dispersion indicating good stability of the system. Subsequently, a hydrophilic sponge was obtained by lyophilization of a gel based on trehalose, Natrosol and PVP-K90, loaded with CUR-NLC and MTR. By compression of the sponge, matrix tablets were obtained and characterized in term of porosity, swelling index, mucoadhesion and drugs release. The ability of the matrix tablets to release CUR and MTR when applied on buccal mucosa and the aptitude of actives to penetrate and/or permeate the tissue were evaluated. The data demonstrate the ability of NLC to promote the penetration of CUR into the lipophilic domains of the mucosal membrane, while MTR can penetrate and permeate the mucosal tissue, where it can perform a loco-regional antibacterial activity. These results strongly support the possibility of using this novel matrix tablet for delivering MTR together with CUR for topical treatment of periodontal diseases.

Resveratrol (RSV) is a natural polyphenol with several interesting broad-spectrum pharmacological properties. However, it is characterized by poor oral bioavailability, extensive first-pass effect metabolism and low stability. Indeed, RSV could benefit from the advantage of the sublingual route of administration. In this view, RSV attitudes to crossing the porcine sublingual mucosa were evaluated and promoted both by six different chemical permeation enhancers (CPEs) as well as by preparing four innovative fast-disintegrating sublingual mini-tablets by spray drying followed by direct compression. Since RSV by itself exhibits a low permeation aptitude, this could be significantly enhanced by the use of CPEs as well as by embedding RSV in a spray-dried powder to be compressed in order to prepare fast-disintegrating mini-tablets. The most promising observed CPEs (menthol, lysine and urea) were then inserted into the most promising spray-dried excipients’ compositions (RSV-B and RSV-C), thus preparing CPE-loaded mini-tablets. However, this procedure leads to unsatisfactory results which preclude the possibility of merging the two proposed approaches. Finally, the best spray-dried composition (RSV-B) was further evaluated by SEM, FTIR, XRD and disintegration as well as dissolution behavior to prove its effectiveness as a sublingual fast-disintegrating formulation.

In recent years, the key role of oxidative stress in pathogenesis of oral diseases has been emphasized and the use of antioxidant agents has been encouraged. Aphanizomenon flos-aquae (AFA) is a unicellular blue-green alga with antioxidant and anti-inflammatory properties. The aim of this study was the formulation and characterization of mucoadhesive thin layer films loaded with AFA, finalized to the treatment of oxidative stress (OS)-related oral diseases. First, to enhance the bioavailability of AFA constituents, the raw food grade material was appropriately treated by a high frequency homogenization able to disrupt cell walls. Thus, Eudragit® E100-based buccal films were produced by the solvent casting method, containing 7% and 18% of AFA. The films, characterized by uniformity in thickness, weight, and drug content, showed low swelling degree, good muco-adhesiveness and controlled drug release. The mechanical tests showed elastic moduli of films of almost 5 MPa that is well-suitable for human buccal applications without discomfort, besides biaxial tests highlighted a marked material isotropy. Permeation studies through porcine mucosae demonstrated the ability of films to promote AFA penetration in the tissues, and when sublingually administered, they produced a drug flux up to six-fold higher than an AFA solution. The new formulations represent an interesting alternative for the development of cosmetics and nutraceuticals with a functional appeal containing plant extracts.