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


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.


CONCLUSIONS
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.
State Engineering Laboratory of Bio-Resources Eco-Utilization, Northeast Forestry University , Harbin , PR China .
Shougang
S
Jiang
Xianfeng
X
Gong
Xiuhua
X
Zhao
Yuangang
Y
Zu
D000818:Animals; D021461:Animals, Outbred Strains; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D001692:Biological Transport; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004337:Drug Carriers / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011897:Random Allocation; D012509:Sarcoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D012709:Serum Albumin / Q000737:chemistry*; D000075462:Serum Albumin, Human; D012995:Solubility; D013499:Surface Properties; D043823:Taxoids / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use
C422455:ALB protein, human; D000970:Antineoplastic Agents; D004337:Drug Carriers; D012709:Serum Albumin; D043823:Taxoids; D000077143:Docetaxel; D005492:Folic Acid; D000075462:Serum Albumin, Human
Antitumor activities; docetaxel; folate; human serum albumin; nanoparticles