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Novel phospholipid-based Labrasol nanomicelles loaded with flavonoids for oral delivery with enhanced penetration and anti-brain tumor efficiency.

BACKGROUND
Owing to the rich anticancer properties of flavonoids, there is the need for their incorporation into delivery vehicles like nanomicelles for safe delivery of the drug into brain tumor microenvironment.


OBJECTIVE
This study therefore aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nanomicelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to target brain tumor. Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in human brain microvascular endothelial cells (HBMECs).


RESULTS
The results demonstrated that Nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the trans epithellal electric resistance (TEER). There was no pathological evidence of renal, hepatic or other organ dysfunction after Nano-flavonoids administration, which showed no significantly influence cytotoxicity to Caco-2 cells.


CONCLUSION
In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance anti-glioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of Nano-flavonoids may ensure optimal therapeutic benefits.