RESUMEN
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.
RESUMEN
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.