Preparation and characterization of parthenolide nanocrystals for enhancing therapeutic effects of sorafenib against advanced hepatocellular carcinoma.

Abstract

A novel nanocrystals delivery system of parthenolide (PTL) was designed to combined application with sorafenib (Sora) for advanced hepatocellular carcinoma (HCC) therapy, attempting to not only improve the poor aqueous solubility of PTL, but also enhance the synergistic therapeutic effects with Sora. The PTL nanocrystals (PTL-NCs) were prepared by precipitation-high-pressure homogenization method. The formed PTL-NCs with rod morphology possessed size of 126.9 ± 2.31 nm, zeta potential of -11.18 ± 0.59 mV and drug loading of 31.11 ± 1.99%. Meanwhile, PTL in PTL-NCs exhibited excellent storage stability and sustained release behavior. The combination therapy of Sora and PTL-NCs (Sora/PTL-NCs) in vitro for HepG2 cells presented superior therapeutic effects over that of individual PTL and Sora on intracellular uptake, cell proliferation inhibition and migration inhibition. Meanwhile the strongest anti-tumor effect with 81.86% inhibition rate and minimized systemic toxicity of Sora/PTL-NCs in vivo were obtained on tumor-bearing mice compared with that of PTL (48.84%) and Sora (58.83%). Thus, these findings suggested that PTL-NCs as an effective delivery system for the synergistically used with Sora to gain an optimal response against HCC, for referenced in the industrialization of nanocrystals products for intravenous administration.

• Authors: Pan Liang, Hangyi Wu, Zhenhai Zhang, Shulong Jiang, Huixia Lv
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 583 Pg. 119375 (Jun 15 2020) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 32344021 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Delayed-Action Preparations
• Sesquiterpenes
• parthenolide
• Sorafenib

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (chemistry, pharmacology)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Delayed-Action Preparations
• Dose-Response Relationship, Drug
• Drug Compounding
• Drug Liberation
• Drug Stability
• Drug Synergism
• Female
• Hep G2 Cells
• Humans
• Liver Neoplasms (drug therapy, pathology)
• Mice, Inbred BALB C
• Mice, Nude
• Nanoparticles
• Sesquiterpenes (chemistry, pharmacology)
• Solubility
• Sorafenib (chemistry, pharmacology)
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays