title: A novel lipid-based nanomicelle of docetaxel: evaluation of antitumor activity and biodistribution.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing, China.
authors: Mingshu
authors: M
authors: Ma
authors: Yanli
authors: Y
authors: Hao
authors: Nan
authors: N
authors: Liu
authors: Zhe
authors: Z
authors: Yin
authors: Lan
authors: L
authors: Wang
authors: Xingjie
authors: X
authors: Liang
authors: Xiaoning
authors: X
authors: Zhang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004355:Drug Stability; D006801:Humans; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008823:Micelles; D057054:Molecular Imaging; D053758:Nanoparticles / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D043823:Taxoids / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D043823:Taxoids; D000077143:Docetaxel