Quantification of DOX bioavailability in biological samples of mice by sensitive and precise HPLC assay

Autor: Chan Zhang, Yifan Wu, Hongying Xu, Liangqi Zhao, Yuefeng Dong
Rok vydání: 2015
Předmět:
Chemistry
Pharmaceutical
Pharmaceutical Science
Uterine Cervical Neoplasms
02 engineering and technology
01 natural sciences
High-performance liquid chromatography
HeLa
Hplc assay
Drug Discovery
polycyclic compounds
Tissue Distribution
Chromatography
High Pressure Liquid
Drug Carriers
Mice
Inbred BALB C
Antibiotics
Antineoplastic
biology
Chemistry
General Medicine
021001 nanoscience & nanotechnology
Area Under Curve
Injections
Intravenous
Molecular Medicine
Female
Drug Monitoring
0210 nano-technology
medicine.drug
Half-Life
Biodistribution
Heart Diseases
Metabolic Clearance Rate
Polyesters
Cmax
Biological Availability
Mice
Nude
macromolecular substances
010402 general chemistry
Risk Assessment
Folic Acid
Pharmacokinetics
medicine
Animals
Humans
Doxorubicin
Pharmacology
Chromatography
technology
industry
and agriculture
biology.organism_classification
Xenograft Model Antitumor Assays
Cardiotoxicity
0104 chemical sciences
Bioavailability
Complementary and alternative medicine
Nanoparticles
HeLa Cells
Zdroj: Pharmaceutical biology. 54(1)
ISSN: 1744-5116
Popis: Doxorubicin (DOX)-loaded folate-targeted poly(3-hydroxybutyrate-co-3-hydroxyoctanoate) [P(HB-HO)] nanoparticles [DOX/FA-PEG-P(HB-HO) NPs] were prepared by the W1/O/W2 solvent extraction/evaporation method for applications in cancer treatment. However, the biodistribution, pharmacokinetics, and targeting of the nanoparticles (NPs) have not yet been studied.The biodistribution, pharmacokinetics, and targeting of DOX/FA-PEG-P(HB-HO) NPs were evaluated in female BALB/c nude mice bearing HeLa tumors.Three DOX formulations were injected into the tail vein of the mice at a dosage of 5 mg/kg. At each time point, blood and various tissues were collected. All samples were then processed and analyzed by a validated high performance liquid chromatographic (HPLC) method.The t1/2 values of DOX/P(HB-HO) NPs and DOX/FA-PEG-P(HB-HO) NPs were 2.7- and 3.5-times higher than that of free DOX. No significant difference (p0.05) was found in Cmax between the NPs and free DOX. The Tmax values of the two NPs were prolonged from 0.25 to 1 h. The AUC0-t values were 1.55- and 3.05-folds higher than that of free DOX, and MRT increased to 15.99 h for DOX/P(HB-HO) NPs and 25.14 h for DOX/FA-PEG-P(HB-HO) NPs. For DOX/FA-PEG-P(HB-HO) NPs, the DOX content in the tumors were 10.81- and 3.33-times higher than those for free DOX and DOX/P(HB-HO) NPs at 48 h, respectively.DOX/FA-PEG-P(HB-HO) NPs displayed reduced cardiac toxicity and improved bioavailability. Moreover, the NPs exhibited a significant extent of DOX accumulation in the tumors, thus suggesting that folate-targeted NPs could effectively transport into HeLa tumors with satisfying targeting.
Databáze: OpenAIRE
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