Advanced search
Start date
Betweenand

Silk fibroin-based delivery systems containing pro-photosensitizing agents for topical photodynamic therapy of wounds

Grant number: 17/18241-5
Support type:Scholarships in Brazil - Master
Effective date (Start): January 01, 2018
Effective date (End): June 30, 2019
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal Investigator:Renata Fonseca Vianna Lopez
Grantee:Iris Sperchi Camilo Brait
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Photodynamic therapy (PDT) is a therapeutic modality for cancer, that involves the application of photosensitizing agents and light. Recently, PDT has been investigated for the treatment of wounds due to its ability to modulate the immune response and its bacteriostatic effect. However, to avoid the typical cell death of the cancer treatment by PDT, the control of the concentration of the photosensitizing agent in the wound and the dose of irradiation need to be carefully studied. Extensive wounds, with areas of hypoxia, common in chronic wounds, also require more detailed investigations, whereas PDT with traditional photosensitizing agents requires the presence of oxygen to be effective. In this context, the objective of this work is to develop drug delivery systems able of releasing constant doses of PDT sensible drugs' in chronic wounds, in the presence and absence of oxygen. To this end, films composed of fibroin conjugated to a nitric oxide donor, the S-nitrosoglutathione (GSNO), containing 5-aminolevulinic acid (5-ALA) will be developed. 5-ALA is a pro-photosensitizer that induces the production of protoporphyrin IX (PpIX) in vivo and is widely used in topical PDT treatment of tumors. GSNO is capable of releasing nitric oxide (NO) and may help in healing wound sites affected by hypoxia. Finally, silk fibroin is a natural biopolymer with properties to support cell growth. The formulations will be characterized by physical and physico-chemical methods and the cytotoxic and phototoxic potential of the films will be evaluated in the presence of different concentrations of 5-ALA and irradiation doses. In vitro evaluation of 5-ALA and NO release profile will be verified using two-compartment vertical diffusion cells, light and coupled NO meter systems. The bactericidal and bacteriostatic activity of the films in the presence of PDT will be verified in strains usually present in chronic wounds. (AU)