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.

The development of efficacious means of delivering antioxidant polyphenols from natural sources for the treatment of skin diseases is of great interest for many cosmetic and pharmaceutical companies. Resveratrol (RSV) and Limonene (LIM) have been shown to possess good anti-inflammatory and antibacterial properties against Staphylococcus aureus infections responsible for many skin disorders, such as acne vulgaris. In this study, solid lipid microparticles are designed as composite vehicles capable of encapsulating a high amount of trans-RSV and enhancing its absorption through the stratum corneum. A microparticulate system based on mixture of PEGylate lipids, long-chain alcohols and LIM is able to entrap RSV in an amorphous state, increasing its half-life and avoiding inactivation due to isomerization phenomena, which represents the main drawback in topical formulations. Particles have been characterized in term of shape, size distribution and drug loading. Antimicrobial tests against S. aureus have highlighted that empty microspheres possess per se antimicrobial activity, which is enhanced by the presence of LIM, demonstrating that they can represent an interesting bactericide vehicle for RSV administration on the skin.

Immediate implant placement is a single-stage restorative approach for missing teeth widely used to overcome the ridge remodeling process occurring after dental extractions. The success of this procedure relies on opportune osseointegration in the surrounding tissues. To support this process, a multifunctional nanocomposite, to be applied in the fresh post-extraction socket, was here designed, prepared, and characterized. This formulation consists of quercetin (QRC)-loaded nanostructured lipid carriers (NLCs) entrapped in a chitosan-based solid matrix containing ciprofloxacin (CPX). QRC-NLCs were prepared by homogenization followed by high-frequency sonication, and thereafter this dispersion was trapped in a chitosan-based CPX-loaded gel, obtaining the nanocomposite powder (BioQ-CPX) by lyophilization. BioQ-CPX displayed desirable properties such as high porosity (94.1 ± 0.5%), drug amounts (2.1% QRC and 3.5% CPX). and low swelling index (100%). Moreover, the mechanism of drug release from BioQ-CPX and their ability to be accumulated in the target tissue were in vitro and ex vivo elucidated, also by applying mathematical models. When trapped into the nanocomposite, QRC stressed under UV light exposure (50 W) was shown to maintain its antioxidant power, and CPX and QRC under natural light were stable over nine months. Finally, both the measured antioxidant power and the antimicrobial and antibiofilm properties on Staphylococcus aureus demonstrated that BioQ-CPX could be a promising platform to support the single-stage dental restorative treatment.

The restoration and prosthetic rehabilitation of missing teeth are commonly performed using dental implants, which are extremely effective and long-lasting techniques due to their osteointegration ability with the preimplant tissues. Quercetin is a phytoestrogen-like flavonoid well known for its several positive effects on human health, mostly linked to the anti-inflammatory, antioxidant, and antibacterial activities against both Gram-positive and Gram-negative bacteria. Moreover, many studies in dentistry and the maxillofacial fields have highlighted the positive effects of quercetin on osteogenesis, acting on osteoblast activity and angiogenetic process, and promoting soft and hard tissue regeneration. This review focuses on the role of quercetin on the healing and restoration of bony defects, considering the experimental findings of its application both in vitro and in vivo as a mere compound or in association with scaffolds and dental implants having functionalized surfaces.

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In an ever-growing perspective of circular economy, the development of conscious, sustainable and environmental-friendly strategies to recycle the waste products is the key point. The scope of this work was to validate the waste bentonite from the grape processing industries as a precious matrix to extract polyphenols by applying a waste-to-market approach aimed at producing novel functional excipients. The waste bentonite was recovered after the fining process and opportunely pre-treated. Subsequently, both the freeze dried and the so-called “wet” bentonites were subjected to maceration. PEG200 and Propylene Glycol were selected as solvents due to their ability to dissolve polyphenols and their wide use in the cosmetic/pharmaceutical field. The extracts were evaluated in terms of yield, density, pH after water-dilution, total phenolic (Folin–Ciocalteu) and protein (Bradford) contents, antioxidant power (DPPH), amount of some representative polyphenols (HPLC-DAD), cytocompatibility and stability. Both solvents validated the bentonite as a valuable source of polyphenols and led to colored fluids characterized by an acidic pH after water-dilution. The best extract was obtained from the wet bentonite with PEG200 and highlighted the highest phenolic content and consequently the strongest antioxidant activity. Additionally, it displayed proliferative properties and resulted almost stable over time. Hence, it might be directly used as polyphenols-enriched functional novel raw material for cosmetic and pharmaceutics purposes.