Preparation, characterization, and antitumor activities of folate-decorated docetaxel-loaded human serum albumin nanoparticles

Abstract

Context: Docetaxel is now a major antitumor drug in clinical use for the treatment of a variety of tumors. The ethanol/Tween 80 solvent required in the formulation to increase the docetaxel solubility is at least partly responsible for the hypersensitivity reaction, decreased uptake by tumor tissue, and increased exposure to other body compartments.

Objective: The present study was aimed at developing hydrosoluble DTX-FA-HSANPs targeting tumor cells and to investigate antitumor activities of the nanoparticles.

Materials and methods: The DTX-HSANPs were prepared using a desolvation technique and the carboxylic groups of NHS-folate were conjugated with the amino groups of the human serum albumin nanoparticles, and studied their size and zeta potential, drug loading efficiency, surface morphology, release properties in vitro, and antitumor activities.

Results: The spherical nanoparticles obtained were negatively charged with a zeta potential of about −30 mV and characterized around 150 nm with a narrow size distribution. Drug loading efficiency was approximately 17.2%. The folate-decorated nanoparticles targeted a human hepatoma cell line effectively. The in vitro drug release of DTX-FA-HSANPs in the first 96 h corresponded with the following equation: Q = 18.87851 − 0.13866t + 0.21276t²− 0.00704t³ + 0.0000847854t⁴− 0.00000034991t⁵ (R²= 0.98155). Moreover, the in vitro antitumor activities of DTX-FA-HSANPs were close to the activities of the positive control (docetaxel). The in vivo inhibition ratios of DTX-FA-HSANPs and docetaxel were 66.2% and 59.5%, respectively, at a dose of 5 mg/kg.

Discussion and conclusion: In light of the observed antitumor activities, it would be of considerable interest to collect sufficient data for the clinical application of docetaxel-loaded nanoparticles.

• Antitumor activities
• docetaxel
• folate
• human serum albumin
• nanoparticles

Acknowledgements

The authors also gratefully acknowledge Mr. Chao Xu, Mr. Yan Hu, and Dr. Dongmei Zhao for technical assistance in experiments.

Declaration of interest

The authors report no conflict of interest in this work. The authors would also like to acknowledge the financial support from, the Fundamental Research Funds for the Central Universities (DL12EA01-03), the Fundamental Research Funds for the Central Universities (DL13CA11), Heilongjiang Postdoctoral Grant (LBH-Z10282), the Special Fund for Forestry Scientific Research in the Public Interest (201204601), the “Twelfth Five-Year” National Science and technology support program in rural areas (2012BAD21B0501-11).