Synthesis and characterization of cannabidiol and tetracycline-loaded nanoemulsions and evaluation of their synergism on antibiofilm and pro-osteogenic effects

• Grant number: 24/15209-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2025
• End date: February 29, 2028
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Denise Madalena Palomari Spolidorio
• Grantee: Maria Júlia Mancim Imbriani
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Nanotechnology has shown advantages in various fields, including healthcare. Nanoemulsion is a system created through nanotechnology that allows drug loading, including the combination of two or more drugs within the same system, offering several advantages such as controlled drug release, greater biocompatibility, and targeted drug delivery to the site of interest. Besides that, natural drugs extracted from plants have been largely used in the health field, due to their biological properties. Cannabis sativa is a plant with several cannabinoids, including cannabidiol, which exhibits therapeutic properties such as anti-inflammatory, regenerative, and antimicrobial effects. However, some limitations are presented against gram-negative bacteria. Periodontal disease is a multifactorial chronic inflammatory, one of the main inflammatory diseases in dentistry. This condition involves a variety of bacteria and immuno-inflammatory events that lead to loss of supportive tissues, resulting in tooth loss. The standard and effective treatment for this disease is biofilm debridement through scaling and root planing. Tetracycline is an antibiotic used to eliminate pathogenic bacteria in various diseases, such as periodontal disease. However, like any antibiotic, its long-term use in high concentrations can cause side effects and bacterial resistance. Finally, there are numerous risk factors for the exacerbation of periodontal disease, with diabetes and smoking being particularly prominent. Conventional cigarette smoking has declined in recent years due to various campaigns. However, in contrast, the use of electronic cigarettes is increasingly encouraged for recreational purposes. It is known that among their side effects is the delay and impairment of tissue regeneration, such as in bone tissue, for example. Therefore, the aim of STUDY 1 will be to evaluate the synergism of cannabidiol and tetracycline against periodontopathogenic bacteria. Subsequently, in STUDY 2, nanoemulsions containing cannabidiol and tetracycline, both separately and together, coated or not with chitosan, will be formulated and characterized, and their effect on bacterial cell membrane permeability will be evaluated using flow cytometry. In STUDY 3, the antibacterial effect of cannabidiol and tetracycline in their free form and encapsulated in nanoemulsions will be assessed, in vitro, against planktonic form and multispecies biofilms of periodontopathogenic bacteria. Finally, in STUDY 4, the osteogenic effect under inflammatory conditions of cannabidiol and tetracycline in their free form and incorporated into nanoemulsions will be evaluated, in vitro, using human Saos-2 osteoblasts under e-cigarette aerosol effects. Statistical analyses will be performed at a significance level of 5% (alpha = 0.05).