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

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.

Materials

Kaempferol (Sigma-Aldrich), caprylic capric acid triglycerides (CCTG) (BrasKem), Compritol® ATO 888 (Gattefossé), polysorbate 20 (Synth), methanol (Supelco), formic acid (Synth), Dialysis bag (Sigma-Aldrich), sepharose CL-4B (Sigma-Aldrich), PBS pH 7.4 (LGC Biotechnology), DiO (3,3′-Dioctadecyloxacarbocyanine perchlorate) (Sigma-Aldrich), cell lines U-87MG and L929 (ATCC), dulbecco′s Modified Eagle′s Medium (DMEM) (Sigma-Aldrich), fetal bovine serum (Sigma-Aldrich)

Luisa Ribeiro Nicoleti, Leonardo Delello Di Filippo, Jonatas Lobato Duarte, Marcela Tavares Luiz, Rafael Miguel Sábio, Marlus Chorilli, Development, characterization and in vitro cytotoxicity of kaempferol-loaded nanostructured lipid carriers in glioblastoma multiforme cells, Colloids and Surfaces B: Biointerfaces, Volume 226, 2023, 113309, ISSN 0927-7765, https://doi.org/10.1016/j.colsurfb.2023.113309.

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