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BIOINSPIRED AND BIOMIMETIC NANOSTRUCTURED SYSTEMS FOR NOSE-TO-BRAIN ADMINISTRATION: A NOVEL PERSPECTIVE FOR GLIOBLASTOMA THERAPY

Grant number: 19/25645-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): October 01, 2020
Effective date (End): September 30, 2022
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal researcher:Valtencir Zucolotto
Grantee:Natália Noronha Ferreira Naddeo
Home Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Glioblastoma (GBM) account for 77% of malignant tumors that occur in the central nervous system (SNC) and, currently, despite all the developments in chemotherapy, radiotherapy, and neurosurgery, GBM still has limited prognosis. The existence of physiological barriers, especially blood brain barriers (BBB), represents the main obstacle that limits adequate concentrations of different drugs designed for therapy. Temozolomide (TMZ) is the first chosen treatment because of its effective antineoplastic activity against high-grade metastatic glioma. However, although the drug is able to cross the BBB, its short half-life requires high orally administered doses in order to ensure therapeutic levels in the brain, which, in turn, causes several side effects. Due to anatomical advantages, an attractive strategy is to use the nasal route of administration, which is appropriate for SNC delivery and avoids the BBB route. However, nose-to-brain delivery bears not only merits but also challenges. Nanotechnology integrates this possibility, giving technological tools and bringing innovative strategies capable of overcoming the main biotechnological limitations. Nanostructured platforms can provide selective drug delivery, enhancing permeability and facilitating drug internalization, promoting drug-controlled release to the intracellular target. Additionally, a novel bioinspired and biomimetic strategy, able to provide therapeutic benefits, includes specific functionalization, applying coating with natural cell membranes. Attempting to stimulate the development of new therapeutic approaches that can improve patient outcomes, we hypothesize that the development of a multifunctional nanostructured delivery system based on polylactic/glycolic acid (PLGA) and chitosan for TMZ encapsulation, can be functionalized by using GBM cell membrane coated technology. The goal is to improve biological response, opening an unprecedented therapeutic opportunity for GBM treatment.

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