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    2020-08-18


    After 24 h from the start of the release test, the cumulative PTX release rate of PTX-micelles at pH 7.4 was 30.8%. This result indicates that PTX was properly encapsulated in micelles. At pH 5.0, the cumulative PTX release rate of PTX-micelles was significantly higher than that at pH 7.4. Therefore, it was suggested that PTX-micelles exist stably in the blood circulation and could release PTX promptly when reaching the periphery of low pH tissue. We considered that this drug release be-havior was useful for treating solid tumors in which tumor tissues can become hypoxic [46]. Slow drug release in the blood of the nano-carrier may also be useful in reducing the side effects of drugs. The results of the degradation test with compound 1 using GPC are shown in Fig. 5. At pH 7.4, the peak of compound 1 exists even after 24 h; however, it was confirmed that the peak disappeared after 24 h at pH 5.0. Although these data support the results of the release test, further investigation will be necessary into the role of lactic Dynasore groups and phosphoesters in promoting the degradation of micelles at low pH.
    3.3. In vitro hemolysis and cytotoxicity of micelles
    Fig. 6a shows the results of the hemolysis test. The hemolysis rate of CrEL was 33.5%–50.2%, whereas that of micelles was 0.8%–1.4%. It was confirmed that the micelle formulation had a significantly lower hemolysis rate and higher biocompatibility than CrEL. As shown in 
    Fig. 6b, at low PTX concentrations, the cell viability of PTX-micelles was significantly higher than that of PTX solution. Since the cell via-bility of drug-free micelles was significantly increased compared with that of CrEL, this result also indicates the safety of micelles as a carrier. At high PTX concentrations, there was no difference in cell viability between PTX-micelles and PTX solution. It was suggested that at rela-tively high PTX concentrations, the influence of PTX on cell viability was greater than that of carrier.
    3.4. Biodistribution of PTX -encapsulated micelles in tumor-bearing mice
    Fig. 7a and b show PTX concentrations of blood, tumor, urine, feces and organs (heart, lungs, liver, stomach, pancreas, spleen, and kidneys). PTX was not detected from the brain. It was assumed that PTX (mole-cular weight: 853.9) prevented the passage of P-glycoprotein through the blood-brain barrier [47]. Since PTX is metabolized in the liver, it was detected in the liver and feces in large amounts. In the group ad-ministered PTX-micelles, the PTX concentration in the tumor and the blood increased by 1.64 and 1.82 times, respectively, as compared with the group Dynasore administered PTX solution. From these results, it was sug-gested that the micelle formulation developed in this study were rela-tively stable in blood circulation and had pH responsiveness in vivo.
    I. Takeuchi and K. Makino
    4. Conclusions
    In this study, we successfully prepared pH-responsive PTX -en-capsulated micelles using a novel phosphoester compound. It was re-vealed that this micelle formulation has biocompatibility and pH-re-sponsiveness. In addition, it was confirmed from the biodistribution study in tumor-bearing mice that this formulation can efficiently deliver PTX to the tumor. These results indicate that this micelle formulation is suitable for treatment of solid tumors and contributes to the reduction of side effects caused by PTX. Further research on micelle formulations with high biocompatibility using phosphoesters would be beneficial in the development of cancer treatment.
    Acknowledgment
    The authors would like to thank R. Mikuni (Tokyo University of Science) for technical assistance with the experiments.
    References
    [9] S.K. Ramadass, N.V. Anantharaman, S. Subramanian, S. Sivasubramanian,
    Contents lists available at ScienceDirect
    Clinical Nutrition ESPEN
    Original article
    Bioelectrical impedance vector analysis (BIVA) as a method to compare body composition differences according to cancer stage and type
    Amara Callistus Nwosu a, b, c, *, Catriona R. Mayland a, b, d, Stephen Mason a, Trevor F. Cox e, Andrea Varro f, Sarah Stanley c, John Ellershaw a, b
    a Palliative Care Institute Liverpool, University of Liverpool, Liverpool, United Kingdom
    b Academic Palliative and End of Life Care Centre, Royal Liverpool and Broadgreen University NHS Hospitals Trust, Liverpool, United Kingdom
    c Marie Curie Hospice Liverpool, Liverpool, United Kingdom
    d Department of Oncology and Metabolism, University of Sheffield, Broom Cross Building, Weston Park Hospital, Whitham Road, Sheffield, United Kingdom
    e Liverpool Cancer Trials Unit, University of Liverpool, Liverpool, United Kingdom
    f School of Physiological Sciences, University of Liverpool, Liverpool, United Kingdom
    Article history:
    Keywords:
    Bioelectrical impedance vector analysis
    Bioelectrical impedance analysis