The effect topical application of rosuvastatin and dexamethasone in osteonecrosis of the jaw induced by bisphosphonate: an in vivo study

• Grant number: 19/09010-5
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2020
• End date: July 31, 2022
• Field of knowledge: Health Sciences - Pharmacy
• Agreement: Cardiff University
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Karina Cogo Müller
• Grantee: Karina Cogo Müller
• Principal researcher abroad: Dr Polina Prokopovich
• Institution abroad: Cardiff University, Wales
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Gilson Cesar Nobre Franco
• Associated research grant: 18/20593-0 - Influence of simvastatin on the mevalonate pathway and the production of bacterial cell wall precursors: an antimicrobial mechanism of action, AP.R

Abstract

The increasing incidence of cases of maxillary osteonecrosis (ONM) has become a concern among health professionals. Its main causes are related to the inhibition of bone remodeling due to osteoclast dysfunction, dysregulated inflammatory processes associated with local infection and impaired angiogenesis. This condition is usually initiated after dental interventions (exodontia and/or implant insertion) in patients taking antireabsorption drugs, with emphasis on bisphosphonates (BFs), which are used in the medical clinic for the treatment of benign or malignant osteometabolic diseases. To date, there is no effective preventive therapy that eliminates or diminishes the risk/severity of ONM. Statins, drugs with lipid-lowering function, have been shown to have positive effects on bone tissue, which may be useful in the therapy of this disease. Rosuvastatin is considered to have a higher anti-inflammatory and antimicrobial potency, has antioxidant and angiogenic properties, as well as increase osteoblasts and provide greater deposition of bone matrix. Another drug that influences bone tissue is dexamethasone, but its relationship with ONM at subacute doses and for topical application has not been established. Therefore, the aim of this study is to develop an improved angiogenic/osteogenic/antimicrobial delivery system for the prevention of osteonecrosis. To achieve this the following objectives are set:1.Develop novel therapeutics formulating through Layer by Layer (LbL) system containing rosuvastatin and dexamethasone (Cardiff University);2.Perform in-vivo efficacy of the therapeutics employing an animal model of maxillary osteonecrosis (ONM);3.Conduct clinical analysis, radiographic and histological analysis; 4.Perform microbiological analyses. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LARISSA, PAVANELLO; GAMBRILL, BENJAMIN; DE CARVALHO, RAFAELA DURRER PAROLINA; DAL PICOLO, MAYARA ZAGUI; CAVALLI, VANESSA; BOARO, LETICIA CRISTINA CIDREIRA; PROKOPOVICH, POLINA; COGO-MUELLER, KARINA. Development, characterization and antimicrobial activity of multilayer silica nanoparticles with chlorhexidine incorporated into dental composites. Dental Materials, v. 39, n. 5, p. 9-pg., 2023-04-27. (19/09010-5)