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Exploring the potential of functionalized nanostructured lipid carriers loaded with cetuximab dispersed in thermo-responsive mucoadhesive hydrogels for the intranasal administration of Cannabis sativa L. oil in the treatment of glioblastoma multiforme.

Grant number: 22/11101-1
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): November 01, 2023
Effective date (End): October 31, 2025
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal Investigator:Marlus Chorilli
Grantee:Jonatas Lobato Duarte
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Glioblastoma multiforme (GBM) is the most prevalent and aggressive neoplasm of the Central Nervous System (CNS). Cannabis sativa L. oil (OC) has emerged as a potential alternative for GBM treatment, as the tumor cells express higher levels of cannabinoid receptors, which are associated with selective apoptosis and cell cycle disruption in neoplastic cells. However, OC faces physical and chemical limitations that hinder its use, such as difficulty in crossing the blood-brain barrier (BBB) and low water solubility, resulting in poor bioavailability. Therefore, further improvements are needed for its clinical application.To overcome the BBB and enhance efficient brain delivery, a promising approach is the encapsulation of OC in functionalized nanostructured lipid carriers (NLCs) that are equipped with specific epidermal growth factor receptor (EGFR) ligands, such as cetuximab (CTX), which are overexpressed in GBM tumor cells. These NLCs will be dispersed in mucoadhesive thermo-responsive hydrogels, aiming for intranasal administration to increase cerebral bioavailability. Thus, the objective of this study is to evaluate the potential of CTX-functionalized NLCs dispersed in mucoadhesive thermo-responsive hydrogels for intranasal administration of OC in GBM treatment.CTX-functionalized NLCs containing OC (NLC-OC-CTX) will be developed using the fusion-emulsification technique followed by sonication, and characterized for their morphology, particle size, polydispersity index, zeta potential, and thermal behavior. The coupling efficiency of CTX to NLCs, as well as its integrity, will also be determined. The NLCs dispersed in mucoadhesive thermo-responsive hydrogels will be characterized for their rheology, mucoadhesion, in vitro release, and ex vivo permeation and retention. The biological potential will be evaluated using in vitro and in vivo models. The goal is to obtain a formulation that facilitates local treatment of the disease, selectively delivers OC to cancer cells, exhibits low systemic toxicity, and demonstrates desirable efficacy.

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