Improved drug targeting to liver tumor by sorafenib-loaded folate-decorated bovine serum albumin nanoparticles

Drug Deliv. 2019 Dec;26(1):89-97. doi: 10.1080/10717544.2018.1561766.

Abstract

Background: To prepare sorafenib-loaded folate-decorated bovine serum nanoparticles (FA-SRF-BSANPs) and investigate their effect on the tumor targeting.

Methods: The nanoparticles were characterized and evaluated by in vivo and in vitro experiments.

Results: SRF-loaded BSA nanoparticles (SRF-BSANPs) was first prepared and modified with folic acid by chemical coupling to obtain FA-SRF-BSANPs. The average particle size, zeta potential, entrapment efficiency, and drug loading of the optimized FA-SRF-BSANPs were 158.00 nm, -16.27 mV, 77.25%, and 7.73%, respectively. The stability test showed that FA-SRF-BSANPs remained stable for more than 1 month at room temperature. The TEM analysis showed that the surface of FA-SRF-BSANPs was nearly spherical. XRD analysis showed that the drug existed in. the nanoparticles in an amorphous state. FA-SRF-BSANPs can promote the intracellular uptake of hepatoma cells (SMMC-7721) with the strongest inhibitory effect compared with SRF-BSANPs and sorafenib solution. Furthermore, the tumor targeting of FA-SRF-BSANPs (Ctumor/Cblood, 0.666 ± 0.053) was significantly higher than those of SRF-BSANPs (Ctumor/Cblood, 0.560 ± 0.083) and sorafenib-solution (Ctumor/Cblood, 0.410 ± 0.038) in nude mice with liver cancer.

Conclusion: FA-modified albumin nanoparticles are good carriers for delivering SRF to the tumor tissue, which can improve the therapeutic effect and reduce the side effects of the drug.

Keywords: Sorafenib; active targeting; albumin nanoparticles; folate; liver tumor.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / metabolism
  • Cattle
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems / methods*
  • Female
  • Folic Acid / administration & dosage*
  • Folic Acid / metabolism
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Mice, Nude
  • Nanoparticles / administration & dosage*
  • Nanoparticles / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Serum Albumin, Bovine / administration & dosage*
  • Serum Albumin, Bovine / metabolism
  • Sorafenib / administration & dosage*
  • Sorafenib / metabolism

Substances

  • Antineoplastic Agents
  • Serum Albumin, Bovine
  • Folic Acid
  • Sorafenib

Grants and funding

The work was supported by a grant from the National Natural Science Foundation of China (No. 81560631), Distinguished Young Scholars Foundation of Jiangxi Province (No. 20162BCB23022), Key research and development program of Jiangxi Province (No. 20171BBG70086).