Development and evaluation of the in vitro biological potential of nanostructured lipid carriers containing doxycycline dispersed in a mucoadhesive thermoresponsive hydrogel for intranasal administration as a treatment for glioblastoma multiforme

• Grant number: 24/15685-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2025
• End date: December 31, 2025
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Jonatas Lobato Duarte
• Grantee: Allana Carolina Leme de Almeida
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Glioblastoma multiforme (GBM) is a lethal brain tumor with a poor prognosis, characterized by a high recurrence and mortality rate. The challenges in treating GBM include the blood-brain barrier (BBB), which hinders drug penetration into the central nervous system (CNS), and resistance to the first-line drug, temozolomide (TMZ). Therefore, research into new treatments that overcome these limitations is necessary. One strategy for finding new therapies is drug repurposing, which aims to discover new therapeutic indications for well-established drugs. In this context, doxycycline (DOX), currently used as a broad-spectrum antibiotic, is a drug of interest due to its antineoplastic action, which works by inhibiting mitochondrial biogenesis. Combined with DOX, the use of nanostructured lipid carriers (NLC) offers advantages such as controlled drug release and the intrinsic ability to cross the BBB. Therefore, this study aims to investigate the cytotoxic efficacy of NLC containing DOX, dispersed in a mucoadhesive thermoresponsive hydrogel for intranasal administration. The NLC will be obtained by the fusion-emulsification technique followed by sonication. The obtained NLC will be characterized in terms of their hydrodynamic diameter, polydispersity index, and zeta potential. The encapsulation efficiency of DOX in the NLC will be determined using high-performance liquid chromatography. The release profile of DOX contained in the NLC or in solution will be determined using a dialysis membrane. The in vitro cytotoxicity of NLC containing DOX will be determined using the U87MG GBM cell line. The mucoadhesive thermoresponsive hydrogels will be formulated and characterized for rheology, mucoadhesive properties, release, and permeation.