[Show abstract][Hide abstract]ABSTRACT: The purpose of the present study was to develop a new method of chemoembolization to improve the therapeutic effectiveness and safety profile of cancer treatment. A chemoembolization approach was designed for human solid tumors using resorbable calcium-phosphate ceramic microspheres loaded with an agent anti-angiogenic to tumor vasculature in vivo. The human uterine sarcoma cell line FU-MMT-3 was used in this study because this tumor is aggressive and also exhibits a poor response to radiotherapy or any chemotherapy currently used. The calcium-phosphate ceramic microspheres loaded with TNP-470, an anti-angiogenic agent, were injected into FU-MMT-3 xenografts in nude mice three times per week for 8 weeks. The treatment using TNP-470-loaded microspheres suppressed tumor growth, compared to treatment with TNP-470 alone, microspheres alone, and the control. The mean tumor weight after treatment using TNP-470-loaded microspheres was significantly lower than that after treatment with microspheres alone. These ceramic microspheres were remarkably embolized in tumor microvessels as well as in the feeding arteries and a significant reduction of intratumoral vascularity was also demonstrated following treatment with TNP-470-loaded microspheres. Severe loss of body weight was not observed in any mice treated with the TNP-470-loaded microspheres, compared to treatment with TNP-470 alone. These results suggest that targeting tumor vasculature in human uterine sarcoma using calcium-phosphate microspheres might be more effective and safer than the treatment that employs anti-angiogenic agent alone. This new chemoembolization method incorporating an anti-angiogenic agent may contribute to the effective treatment of locally advanced or recurrent solid tumors.
(Cancer Sci 2010; 101: 984–990)
[Show abstract][Hide abstract]ABSTRACT: We have successfully synthesized hollow biphasic calcium-phosphate microspheres consisting of the β-tricalcium phosphate (β-Ca 3(PO4)2; β-TCP) and calcium-deficient hydroxyapatite (DAp) using an ultrasonic spray-pyrolysis technique. The resulting hollow biphasic microspheres have been applied as a carrier of a drug delivery system (DDS) for medical treatment of cancers. An anti-angiogenic agent, TNP-470 (Takeda), was used as one of drug models. We have performed biological evaluations in vitro and in vivo using the biodegradable calcium-phosphate microsphere loaded with TNP-470. The results of in vitro and in vivo testing indicate that the microspheres loaded with TNP-470 inhibit i) the proliferation of FU-MMT-3 cells as a tumor model and ii) the enlargement of tumor sizes as a model of nude mice injected with FU-MMT-3 cells. The biological evaluations demonstrate that the present microspheres loaded with TNP-470 have an excellent anti-tumorigenesis effect.
No preview · Article · Jan 2008 · Key Engineering Materials
[Show abstract][Hide abstract]ABSTRACT: We synthesized tricalcium phosphate (TCP) microspheres using an ultrasonic spray-pyrolysis technique, and investigated the effect of the concentrations of the starting solution on the powder properties. The XRD pattern showed that the crystalline phases of the resulting powders were β-TCP/HAp biphase in the case of pyrolysis temperature at 850°C and TCP single phase at 1000°C. The Ca/P molar ratios were determined by XRF to be at 1.50 ±0.03. The particle shapes of the powders were observed by SEM; the diameters of the microspheres were narrowly distributed from 0.5 to 4 μm. The mean particle diameters of the resulting powder increased with the concentration of the starting solutions and could be controlled in the range of 0.85-1.4 μm. When the compressed powder was sintered at 1050°C for 5 h, the relative density of the sintered compact attained to 97%. The TCP microspheres had good sinterability.
No preview · Article · Jan 2006 · Key Engineering Materials
[Show abstract][Hide abstract]ABSTRACT: We performed to synthesize the calcium-phosphate microsphere with well-controlled particle size by changing the frequency of the ultrasonic transducer. The crystalline phases of the resulting powders were composed of β-tricalcium phosphate (β-TCP) and hydroxyapatite (HAp); the Ca/P molar ratios were about 1.50. The SEM observation indicated that the resulting powders were composed of microspheres with a diameter of ~1 to ~2.5 μm. The particle sizes increased with decreasing ultrasonic frequency, and the distributions were quite narrow. The above results show that the particle size can be easily controlled by changing the frequency of ultrasonic transducer during spray-pyrolysis.
Preview · Article · Jan 2005 · Phosphorus Research Bulletin