ANTIBACTERIAL, IMMUNOMODULATORY AND HEALING ACTION OF A STANDARDIZED EXTRACT OF RED PROPOLIS AND BENZOPHENONE-ENRICHED FRACTION: COMPUTATIONAL PREDICTIONS AND DEVELOPMENT OF A TOPICAL PRODUCT FOR TREATING CUTANEOUS INFECTIONS

• Grant number: 23/01436-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2023
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Ethnopharmacology
• Principal Investigator: Claudia Helena Pellizzon
• Grantee: Nicolas Ripari
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant: 17/04138-8 - Attainment of chemical, analytical, biological, pharmacological and technological studies to fill the gaps on the development of Brazilian propolis sector, AP.TEM

Abstract

Wound healing is a challenge in hospital environments currently faced in clinical medicine due to tissue infections by multidrug-resistant bacteria, especially in individuals with comorbidities who develop pressure ulcers (PU). Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium that causes such infections, which can lead to limb amputation in diabetic individuals. Thus, the search for new antimicrobials is urgent and natural products such as propolis are sources of molecules with well-known antibacterial action. During the candidate's PhD, the strong anti-MRSA action of red propolis was shown and its compounds were analyzed in silico on MRSA penicillin binding protein 2a (PBP2a) enzyme, which may be a possible target of Brazilian red propolis components such as benzophenones involved in their mechanism of action. The goal of this project is to evaluate the antimicrobial, immunomodulatory and healing effects standardized red propolis extract (SRPE) and benzophenone-enriched fraction (BRF), aiming at developing a topical product for the treatment of difficult-to-heal wounds, such as PU. This project comprises three phases, involving two universities of São Paulo State and three full professors: phase I will be dedicated to the antibacterial activity of SRPE and BRF, as well as their possible synergism with antimicrobials (imipenem and ertapenem) for the production of pre-formulations that will be assessed in macrophages, evaluating the immunomodulatory effect and the microbicidal capacity of these cells. These pre-formulations will also be tested for cell regeneration in vitro in 2D and 3D cultures using fibroblasts and keratinocytes. Phase II will be dedicated to elucidate the mechanism of action of benzophenones found in EPPV and FRB (guttiferone and oblongifolin) by in silico analysis of molecular docking and molecular dynamics in PBP2a. Phase III will include the development of a topical product with the best pre-formulation and skin permeation assessment. The development of this project may result in patent and/or further clinical trials.