Baicalin lipid nanocapsules for treatment of glioma: characterization, mechanistic cytotoxicity, and pharmacokinetic evaluation

ABSTRACT

Objectives

Baicalin is a promising anticancer nutraceutical compound, but its application is hindered by its low water solubility and bioavailability, which can be remedied by its encapsulation in nanoparticles.

Methods

Lipid nanocapsules (LNCs) were developed to enhance baicalin delivery via intravenous and intranasal routes, and potentiate its therapeutic activity in treatment of glioma.

Results

LNCs displayed a particle size of 17.76 nm and sustained release of 74.36% after 24 h. The IC50 of baicalin LNCs (13 ± 5 µg/ml) was 60 times lower than free baicalin (780 ± 107 µg/ml) on human glioblastoma multiform cell line U87, with adequate cellular uptake as delineated by confocal laser microscopy. Both baicalin and LNCs induced cell cycle arrest at S and G2/M phases, with significant up-regulation in P21 gene, and decline in Nrf-2, HO-1 and VEGF gene expression. LNCs increased baicalin’s bioavailability, either after intravenous (AUC0-24 h 10.94 ± 0.28 vs 3.53 ± 0.09 µg/ml*h), or intranasal administration (AUC0-24 h 6.26 ± 0.11 vs 3.17 ± 0.04 µg/ml*h). They also bypassed the blood brain barrier and achieved significantly higher brain delivery compared to free baicalin (drug targeting efficiency 160.73% vs 52.9%).

Conclusion

Baicalin LNCs is a promising treatment modality for glioma, when administered through intravenous or intranasal routes.

KEYWORDS:

• Scutellaria baicalensis
• nanoparticles
• brain
• cancer
• pharmacokinetics
• nutraceutical

Acknowledgments

The paper is based upon work supported by Science, Technology & Innovation funding Authority (STDF), project number 43686 (Maha Nasr). Sara A. Abdel Gaber would like to thank Annette Boese (Drug Delivery across biological barrier research group at Helmholtz Institute for Pharmaceutical research Saarland) for her generous help in capturing the confocal laser scanning microscope images, and both Annette Boese and Sara Nasr from the same research group for operating the flow cytometer. Sara A. Abdel Gaber would like to acknowledge the PhosAgro/UNESCO/IUPAC research grant in green chemistry (received in 2019) which permitted inter alia her stay at the Helmholtz Institute for Pharmaceutical Sciences Saarland (HIPS). Ibrahim El-Sherbiny would like to thank the Science, Technology and Innovation Funding Authority (STIFA), Egypt (Capacity Building Fund, CB-22808).

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Author contributions

All authors were involved in the conception, design, analysis and interpretation of data, as well as drafting the paper and its critical revision. All authors agree to be accountable for all aspects of the work and they all approve the final version of the paper.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17425247.2022.2139370

Additional information

Funding

The paper was supported by Science, Technology & Innovation funding Authority (STDF), under grant number 43686.