Herpetetrone nanosuspensions enhance drug solubility and bioavailability to improve anti-hepatic fibrosis effects

Abstract

The aim of this study was to enhance the dissolution rate and oral bioavailability of herpetetrone (HPT) by preparing nanosuspensions (NSs) and evaluate the changes in its anti-hepatic fibrosis effect. Herpetetrone nanosuspension (HPT-NS) was prepared using the ultrasound-precipitation technique, and characterised on the basis of mean diameter, zeta potential (ZP), encapsulation efficiency percent (EE%), scanning electron microscopy (SEM), and X-ray powder diffraction (XRPD). In addition, the pharmacokinetics and anti-hepatic fibrosis activity were evaluated. HPT-NS prepared with the optimised formulation was found to be spherical with mean diameter of 177.48 ± 6.13 nm, polydispersity index (PDI) of 0.108 ± 0.002 and ZP of −17.28 ± 2.02 mV. The EE (m/m, %) was 83.25 ± 0.27. XRPD analyses confirmed that the amorphous state of HPT in HPT-NS remained unchanged. The dissolution rate of HPT-NS was significantly higher than that of HPT coarse suspensions (HPT-CSs). Following oral administration, C_max and AUC_0–t of HPT-NS showed a significant increase (p < 0.05). In vitro, HPT inhibited the proliferation of HSC-T6 cells and induced apoptosis by up-regulating the expression of Bax proteins and down-regulating the expression of Bcl-2 and TGF-β1 proteins. Compared with HPT-CS, HPT-NS exhibited a more pronounced anti-fibrotic effect. HPT-NS, as a new drug formulation designed to improve the solubility and bioavailability of the drug, shows promising potential in enhancing the anti-liver fibrosis effect.

Keywords:

• Herpetetrone
• nanosuspension
• ultrasound-precipitation technique
• dissolution
• HSC-T6 cells proliferation inhibition

Author contributions

The work was done jointly by all the authors. The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Yuji Zhong: investigation, experiment, and writing – original draft. Fang Wang and Yuye Xue: investigation and experiment. Baode Shen: investigation and supervision. Chengying Shen: supervision and funding acquisition. Haiqiang Jia: investigation and experiment. Lingyu Hang: experiment, writing – review and editing, and supervision. Liqiang Wang: supervision and project administration. Hailong Yuan: supervision, project administration, and funding acquisition.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (81873092, 82174074, and 81803741).