Formulation, characterization, and geno/cytotoxicity studies of galbanic acid-loaded solid lipid nanoparticles

Abstract

Context: Galbanic acid (GBA) is a sesquiterpene coumarin with different medicinal properties and anticancer effects.

Objective: To improve the anticancer activities of GBA, in the current study, we aimed to fabricate GBA-loaded solid lipid nanoparticles (GBA-SLNs) and study their biological activities in vitro.

Materials and methods: Hot homogenization was used for preparation of GBA-SLNs. The encapsulation efficiency (EE) and drug loading (DL) and in vitro release were determined. MTT, DAPI, DNA fragmentation, comet, and Anexin V apoptosis assays were used to compare the anti-cell proliferation and genotoxicity properties of GBA and GBA-SLNs against A549 cells and HUVEC to detect apoptosis and DNA damage in the final concentration of 100 µM after 48 h treatment.

Results: Scanning electron microscopy (SEM) and particle size analysis showed spherical SLNs (92 nm), monodispersed distribution, and zeta potential of −23.39 mV. High EE (>98%) and long-term in vitro release were achieved. The stability of GBA-SLNs in aqueous medium was approved after 3 months in terms of size and polydispersity index. GBA was able to inhibit A549 growth with an IC₅₀ value of 62 µM at 48 h. Although GBA-SLNs could also inhibit the growth rate of A549 cells, the effect is perceived after 48 h, as approved by the quantitative expression of Bcl-xL and Casp 9 genes, and also genotoxicity assays.

Conclusion: Long-term apoptotic effect of GBA-SLNs compared with GBA may be due to the accumulation of GBA-SLNs in the tumor site because of deviant tumor pathology. Our data confirmed that SLNs could be exploited for sustained lipophilic GBA delivery.

• Anticancer
• Ferula ovina
• galbanic acid
• sesquiterpene coumarin
• sustained drug delivery

Declaration of interest

The authors declare that there are no conflicts of interest. Authors would like to thank Research Center for Pharmaceutical Nanotechnology (RCPN), Tabriz University of Medical Sciences, Tabriz, Iran, for supporting this project (Grant no. 90011, which is a part of PhD thesis no. 90/011/101/1).