Utilize este identificador para referenciar este registo: https://hdl.handle.net/10316/111211
Título: A two-pronged approach against glioblastoma: drug repurposing and nanoformulation design for in situ-controlled release
Autor: Mendes, Maria 
Branco, Francisco
Vitorino, Rui
Sousa, João 
Pais, Alberto 
Vitorino, Carla 
Palavras-chave: Drug repurposing; Bioinformatics; Ultra-small nanostructured lipid carriers; Thermoresponsive matrix; In situ controlled release
Data: Dez-2023
Editora: Springer Publishing Company
Projeto: UID/QUI/00313/2020 
UIDB/04501/2020 
UIDP/04501/2020 
POCI-01-0145-FEDER-007628 
SFRH/BD/133996/2017 
COVID/BD/152172/2021 
Título da revista, periódico, livro ou evento: Drug Delivery and Translational Research
Volume: 13
Número: 12
Resumo: Glioblastoma (GB) is one of the most lethal types of neoplasms. Its biologically aggressive nature and the presence of the blood-brain barrier (BBB) limit the efficacy of standard therapies. Several strategies are currently being developed to both overcome the BBB and deliver drugs site specifically to tumor cells. This work hypothesizes a two-pronged approach to tackle GB: drug repurposing with celecoxib (CXB) and a nanoformulation using ultra-small nanostructured lipid carriers (usNLCs). CXB antitumor druggable activity was inspected bioinformatically and screened in four glioma cell lines aiming at the comparison with temozolomide (TMZ), as standard of care. Delving into formulation design, it was tailored aiming at (i) improving the drug solubility/loading properties, (ii) assigning a thermal-triggerable drug release based on a lipid matrix with a low melting point, and (iii) enhancing the cytotoxic effect by selecting a template targetable to tumor cells. For this purpose, an integrated analysis of the critical material attributes (CMAs), critical process parameters (CPPs), and critical quality attributes (CQAs) was conducted under the umbrella of a quality by design approach. CMAs that demonstrate a high-risk level for the final quality and performance of the usNLCs include the drug solubility in lipids (solid and liquid), the lipid composition (envisioning a thermoresponsive approach), the ratio between lipids (solid vs. liquid), and the surfactant type and concentration. Particle size was shown to be governed by the interaction lipid-surfactant followed by surfactant type. The drug encapsulation did not influence colloidal characteristics, making it a promising carrier for lipophilic drugs. In general, usNLCs exhibited a controlled drug release during the 72 h at 37 °C with a final release of ca. 25%, while at 45 °C this was doubled. The in vitro cellular performance depended on the surfactant type and lipid composition, with the formulations containing a sole solid lipid (Suppocire® NB) and Kolliphor® RH40 as surfactant being the most cytotoxic. usNLCs with an average diameter of ca. 70 nm and a narrow size distribution (PdI lower than 0.2) were yielded, exhibiting high stability, drug protection, sustained and thermo-sensitive release properties, and high cytotoxicity to glioma cells, meeting the suitable CQAs for parenteral administration. This formulation may pave the way to a multi-addressable purpose to improve GB treatment.
URI: https://hdl.handle.net/10316/111211
ISSN: 2190-393X
2190-3948
DOI: 10.1007/s13346-023-01379-8
Direitos: openAccess
Aparece nas coleções:FCTUC Química - Artigos em Revistas Internacionais
FFUC- Artigos em Revistas Internacionais

Mostrar registo em formato completo

Visualizações de página

127
Visto em 5/nov/2024

Downloads

51
Visto em 5/nov/2024

Google ScholarTM

Verificar

Altmetric

Altmetric


Este registo está protegido por Licença Creative Commons Creative Commons