Development, characterization and in vitro cytotoxicity of kaempferol-loaded nanostructured lipid carriers in glioblastoma multiforme cells

Author(s)

Nicoleti, Luisa Ribeiro ; Di Filippo, Leonardo Delello ; Duarte, Jonatas Lobato ; Luiz, Marcela Tavares ; Sabio, Rafael Miguel ; Chorilli, Marlus

• Document type: Journal article
• Source: COLLOIDS AND SURFACES B-BIOINTERFACES; v. 226, p. 7-pg., 2023-04-11.

Abstract

Glioblastoma multiforme is the most common and most aggressive human brain cancer. GBM treatment is still a challenge because many drugs are not able to cross the blood-brain barrier, in addition to the increasing resistance to currently available chemotherapy. New therapeutic alternatives are emerging, and, in this context, we highlight kaempferol, a flavonoid with remarkable anti-tumor activity but with limited bioavailability due to its strong lipophilic property. A promising tool to improve the biopharmaceutical properties of molecules such as kaempferol is the use of drug-delivery nanosystems, such as nanostructured lipid carriers (NLC), which can facilitate the dispersion and delivery of highly lipophilic molecules. The present work aimed at the development and characterization of kaempferol-loaded NLC (K-NLC) and the evaluation of its biological properties using in vitro models. The K-NLC showed an average size of 120 nm, zeta potential of - 21 mV, and polydispersity index of 0.099. The K-NLC presented high kaempferol encapsulation efficiency (93%), a drug loading of 3.58%, and a sustained kaempferol release profile for up to 48 h. In addition to presenting a 7-fold increase in kaempferol cytotoxicity, its encapsulation in NLC promoted a cellular uptake of 75%, which corroborates with increased cytotoxicity in U-87MG cells, as observed. Together, these data reinforce the promising antineoplastic properties of kaempferol in addition to the key role of NLC as a platform for the efficient delivery of lipophilic drugs to neoplastic cells, which improved their uptake and therapeutic efficacy in glioblastoma multiforme cells. (AU)

• FAPESP's process: 19/25125-7 - Nanoemulsions containing terpenes as potentials larvicides and repellents against Aedes aegypti (Linnaeus, 1762)
• Grantee: Jonatas Lobato Duarte
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/17913-5 - Pharmacotechnical development and in vitro and in vivo anti-Candida albicans activity of nanostructured lipid carriers dispersed in hydrogels for vaginal administration of hypericin
• Grantee: Marlus Chorilli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/12622-0 - Evaluation of the biological potential of nanostructured lipid carriers functionalized with cetuximab dispersed in mucoadhesive thermo-responsive hydrogels for intranasal administration of temozolomide in the treatment of Glioblastoma Multiforme
• Grantee: Leonardo Delello Di Filippo
• Support Opportunities: Scholarships in Brazil - Doctorate