Nanostructured multifunctional systems for drug controlled release through nasal route on glioblastomas treatment

• Grant number: 16/09671-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): July 01, 2017
• Effective date (End): March 31, 2020
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Maria Palmira Daflon Gremião
• Grantee: Natália Noronha Ferreira Naddeo
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated scholarship(s): 18/04546-1 - Evaluation of synergic effect between CHC and cetuximab against glioblastoma using drug delivery systems, BE.EP.DR

Abstract

Glioblastomas (GBM) account 77% of malignant tumors that occurs on central nervous system (SNC) and today, despite all advances in chemotherapy, radiotherapy and neurosurgery, remains with limited prognoses. The existence of physiological barriers, especially blood brain barrier (BBB), represents the main obstacle that limits appropriate concentrations of the drugs designed to GBM therapy. Due their anatomical advantages, a strategy propose for appropriate delivery of therapeutic agents to SNC involves the use of nasal route of administration once it avoids the passage through the BBB, allowing appropriated drug concentrations reach the brain by perineural channels. In parallel, the understanding about molecular features of tumor cells combined with biophysics, chemistry and pharmacology research suggests that therapy of cancer pathology should include multiple target approach, which provides simultaneous interference on different signaling pathways, minimizing the occurrence of resistance. Nanotechnology integrates these research giving technological tools that might provide selective drug delivery, facilitate drug internalization and promote therapeutic agent controlled release against the intracellular target. Fallowing this rationality, this research project proposes rational design of multifunctional nanoparticles combining the use of alginate and chitosan polymers due their mucoadhesive properties and ability to interact with mucus constituents; a combination of cetuximab drug, monoclonal antibody against epidermal growth factor receptor which inhibit the production of pro-angiogenic factors and alpha-cyano-4-hydroxycinnamic acid (CHC), wich prevent monocarboxylate transporters (MCTs) activity responsible for lactate efflux to extracellular medium, promoting tumor cells death by acidosis and advantages offered by nasal route to reach SNC, allowing a new and favorable future on GBM treatment. (AU)

Scientific publications

(6)

(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)

FERREIRA, NATALIA N.; GRANJA, SARA; BONI, FERNANDA ISADORA; FERREIRA, LEONARDO M. B.; REIS, RUI M.; BALTAZAR, FATIMA; GREMIAO, MARIA PALMIRA D.. A novel strategy for glioblastoma treatment combining alpha-cyano-4-hydroxycinnamic acid with cetuximab using nanotechnology-based delivery systems. DRUG DELIVERY AND TRANSLATIONAL RESEARCH, v. 10, n. 3, SI, JAN 2020. (18/04546-1, 17/16324-0, 16/09671-3)

VICTORELLI, FRANCESCA DAMIANI; DE OLIVEIRA CARDOSO, VALERIA MARIA; FERREIRA, NATALIA NORONHA; FIORAMONTI CALIXTO, GIOVANA MARIA; FONTANA, CARLA RAQUEL; BALTAZAR, FATIMA; DAFLON GREMIAO, MARIA PALMIRA; CHORILLI, MARLUS. Chick embryo chorioallantoic membrane as a suitable in vivo model to evaluate drug delivery systems for cancer treatment: A review. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, v. 153, p. 273-284, AUG 2020. (14/50928-2, 19/07245-5, 18/04546-1, 13/01565-1, 16/09671-3, 15/21412-0, 16/06337-5, 17/10016-2, 17/23357-2)

FERREIRA, LEONARDO M. B.; ALONSO, JOVAN D.; KIILL, CHARLENE P.; FERREIRA, NATALIA N.; BUZZA, HILDE H.; MARTINS DE GODOI, DENIS R.; DE BRITTO, DOUGLAS; ASSIS, ODILIO BENEDITO G.; SERAPHIM, THIAGO V.; BORGES, JULIO CESAR; et al. Exploiting supramolecular interactions to produce bevacizumab-loaded nanoparticles for potential mucosal delivery. EUROPEAN POLYMER JOURNAL, v. 103, p. 238-250, JUN 2018. (12/13446-4, 16/09671-3, 17/16324-0, 12/10174-3)

FERREIRA, NATALIA N.; DE OLIVEIRA JUNIOR, EDILSON; GRANJA, SARA; BONI, I, FERNANDA; FERREIRA, LEONARDO M. B.; CURY, BEATRIZ S. F.; SANTOS, LILIAN C. R.; REIS, RUI M.; LIMA, ELIANA M.; BALTAZAR, FATIMA; et al. Nose-to-brain co-delivery of drugs for glioblastoma treatment using nanostructured system. International Journal of Pharmaceutics, v. 603, JUN 15 2021. (16/09671-3)

RIBEIRO DE SOUZA, ANA LUIZA; FERREIRA AMORIM, AMANDA CLAUDIA; CINTRA, EMILIO RAMOS; FERREIRA, NATALIA NORONHA; DANTAS SILVA, LUIS ANTONIO; HAYASAKI, TACIO GONCALVES; ALMEIDA DINIZ, DANIELLE GUIMARAES; LIMA, ELIANA MARTINS. Development and validation of a rapid RP-HPLC method for simultaneous quantification of paclitaxel and cetuximab in immunoliposomes. Talanta, v. 225, APR 1 2021. (18/04546-1, 16/09671-3)

DE OLIVEIRA CARDOSO, VALERIA MARIA; PEREIRA DE BRITO, NATALIA ARAUJO; FERREIRA, NATALIA NORONHA; BONI, FERNANDA ISADORA; BARBOZA FERREIRA, LEONARDO MIZIARA; CARVALHO, SUZANA GONCALVES; DAFLON GREMIAO, MARIA PALMIRA. Design of mucoadhesive gellan gum and chitosan nanoparticles intended for colon-specific delivery of peptide drugs. COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS, v. 628, NOV 5 2021. (14/50928-2, 16/09671-3, 15/21412-0, 18/04546-1)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

NADDEO, Natália Noronha Ferreira. Nanostructured multifunctional systems for drug release through the nasal route applied on glioblastoma treatment. 2020. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Faculdade de Ciências Farmacêuticas. Araraquara Araraquara.