HYDROGENLS CONFINED IN 3D PRINTED MATRIX TO CONTROLLED AND SITE-SPECIFIC DELIVERY OF INGENOL-3-DODECANOATE AND FLUOROCHROME FOR PHOTODIAGNOSTIC AND THERAPY OF CEREBRAL TUMORS

• Grant number: 20/04507-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2021
• End date: May 31, 2023
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Antonio Claudio Tedesco
• Grantee: Italo Rodrigo Calori
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Glioblastoma multiforme (GBM) are brain tumors considered incurable. Current treatmentwith the chemotherapy drug Temozolomide (TMZ) has a high rate of resistance and difficultyin crossing the blood-brain barrier (BBB). Drug delivery implants in the brain region are newpharmacological alternatives that avoid the need for BBB permeation. In a recent study, thecompound ingenol-3-dodecanoate (IngC) presented an efficiency of more than 100 timesagainst some gliomas when compared to TMZ [1]. In parallel, fluorochromes have been usedin photodiagnosis and in resection guided by intraoperative fluorescence of brain tumors. Thus,the association of IngC and fluorochromes in controlled-release polymeric implants is a newand promising strategy for the treatment of GBM. In this project, an implant will be structuredfrom a hydrogel coated with an impermeable polymeric membrane open at the ends foradministration by implant after surgical resection. Adjusting the opening diameter seeks tooptimize the asset release rate. Thus, the aims of this project are: (i) to develop a 3D implantfor in situ release of IngC and fluorochrome; (ii) to control the rate of release of assets; (iii) toevaluate the antineoplastic effect of the system against GBM; (iv) to demonstrate the system'scapacity for photodiagnosis in order to monitor the evolution / remission of the tumor in realtime throughout the treatment; (v) to evaluate in vivo the rate of degradation of the implants aswell as the biodistribution of the assets in the brain region.

Scientific publications

(5)

(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)

MONICO, DANIELLI AZEVEDO; CALORI, ITALO RODRIGO; SOUZA, CARLA; ESPREAFICO, ENILZA MARIA; BI, HONG; TEDESCO, ANTONIO CLAUDIO. Melanoma spheroid-containing artificial dermis as an alternative approach to in vivo models. Experimental Cell Research, v. 417, n. 1, p. 11-pg., 2022-05-20. (20/04507-6, 13/50181-1, 17/01272-5)

CALORI, ITALO RODRIGO; ALVES, SAMARA RODRIGUES; BI, HONG; TEDESCO, ANTONIO CLAUDIO. Type-I Collagen/Collagenase Modulates the 3D Structure and Behavior of Glioblastoma Spheroid Models. ACS APPLIED BIO MATERIALS, v. 5, n. 2, p. 11-pg., 2022-02-21. (20/04507-6, 13/50181-1)

CALORI, ITALO RODRIGO; PINHEIRO, LUKAS; BRAGA, GUSTAVO; PEDROSO DE MORAIS, FLAVIA AMANDA; CAETANO, WILKER; TEDESCO, ANTONIO CLAUDIO; HIOKA, NOBORU. Interaction of triblock copolymers (Pluronic (R)) with DMPC vesicles: a photophysical and computational study. SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY, v. 275, p. 10-pg., 2022-07-05. (20/04507-6, 13/50181-1)

ALVES, SAMARA RODRIGUES; CALORI, ITALO RODRIGO; TEDESCO, ANTONIO CLAUDIO. Photosensitizer-based metal-organic frameworks for highly effective photodynamic therapy. Materials Science & Engineering C-Materials for Biological Applications, v. 131, DEC 2021. (20/04507-6, 13/50181-1)

CALORI, ITALO RODRIGO; BRAGA, GUSTAVO; TESSARO, ANDRE LUIZ; CAETANO, WILKER; TEDESCO, ANTONIO CLAUDIO; HIOKA, NOBORU. Self-aggregation of the proteolytic forms of Verteporfin: An in silico and in vitro study. JOURNAL OF MOLECULAR LIQUIDS, v. 352, p. 9-pg., 2022-02-14. (20/04507-6, 13/50181-1)