A novel lipid-based nanomicelle of docetaxel: evaluation of antitumor activity and biodistribution
Open Access
- 1 July 2012
- journal article
- research article
- Published by Informa UK Limited in International Journal of Nanomedicine
- Vol. 7, 3389-3398
- https://doi.org/10.2147/IJN.S29827
Abstract
Purpose: A lipid-based, nanomicelle-loaded docetaxel (M-DOC) was designed and characterized. Optical imaging was employed to evaluate the pharmacokinetics and antitumor efficacy of docetaxel in vivo. Materials and methods: The M-DOC was prepared using the emulsion-diffusion method. Transmission electron microscopy and dynamic light scattering were used to assess the morphology and particle size of the M-DOC. Critical micelle concentrations, their stability under physiological conditions, and their encapsulation efficiency – as measured by high-performance liquid chromatography – were assessed. Pharmacological features were evaluated in two different animal models by comparing M-DOC treatments with docetaxel injections (I-DOC). Bioluminescence imaging was used to assess antitumor activity and docetaxel distribution in vivo, using nude mice injected with luciferase-expressing MDA-MB-231 human breast tumor cells. In addition, animals injected with B16 melanoma cells were used to measure survival time and docetaxel distribution. Results: The M-DOC was prepared as round, uniform spheres with an effective diameter of 20.8 nm. The critical micelle concentration of the original emulsion was 0.06%. Satisfactory encapsulation efficiency (87.6% ± 3.0%) and 12-hour stability were achieved. Xenograft results demonstrated that the M-DOC was more effective in inhibiting tumor growth, without significantly changing body weight. Survival was prolonged by 12.6% in the M-DOC group. Tumor growth inhibitory rates in the M-DOC and I-DOC groups were 91.2% and 57.8% in volume and 71.8% and 44.9% in weight, respectively. Optical bioluminescence imaging of tumor growths yielded similar results. Area under the curve(0–6 hour) levels of docetaxel in blood and tumors were significantly higher in the M-DOC group (15.9 ± 3.2 µg/mL-1, 601.1 ± 194.5 µg/g-1) than in the I-DOC group (7.2 ± 1.7 µg/mL-1, 357.8 ± 86.2 µg/g-1). The fluorescent dye 1,1-dioctadecyl-3,3,3,3’-tetramethylindotricarbocyanine iodide mimicked M-DOC in optical imaging, and accumulated more in tumors in comparison with I-DOC. Conclusion: These results suggest that the lipid-based nanomicelle system was effective in inhibiting tumor growth, with little toxicity. Moreover, we have developed a noninvasive optical imaging method for antitumor drug evaluation, which merits further analysis for potential clinical applications.Keywords
This publication has 29 references indexed in Scilit:
- Recent developments in lipid-based pharmaceutical nanocarriersFrontiers in Bioscience-Landmark, 2011
- Advances in polymeric micelles for drug delivery and tumor targetingNanomedicine: Nanotechnology, Biology and Medicine, 2010
- Strategies in the design of nanoparticles for therapeutic applicationsNature Reviews Drug Discovery, 2010
- A phase 2 study of SP1049C, doxorubicin in P-glycoprotein-targeting pluronics, in patients with advanced adenocarcinoma of the esophagus and gastroesophageal junctionInvestigational New Drugs, 2010
- The whole pictureNature, 2010
- Docetaxel-related side effects and their managementEuropean Journal of Oncology Nursing, 2009
- Multicenter phase II trial of Genexol-PM, a Cremophor-free, polymeric micelle formulation of paclitaxel, in patients with metastatic breast cancerBreast Cancer Research and Treatment, 2007
- Alternative drug formulations of docetaxel: a reviewAnti-Cancer Drugs, 2007
- Micellar Nanocontainers Distribute to Defined Cytoplasmic OrganellesScience, 2003
- Solutol HS 15, nontoxic polyoxyethylene esters of 12-hydroxystearic acid, reverses multidrug resistance.1991