Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1993 Apr;67(4):668–673. doi: 10.1038/bjc.1993.124

Implantation treatment method of slow release anticancer doxorubicin containing hydroxyapatite (DOX-HAP) complex. A basic study of a new treatment for hepatic cancer.

K Kunieda 1, T Seki 1, S Nakatani 1, M Wakabayashi 1, T Shiro 1, K Inoue 1, M Sougawa 1, R Kimura 1, K Harada 1
PMCID: PMC1968362  PMID: 8471423

Abstract

We performed an experimental study on slow releasing anticancer drug implantation treatment as a new therapy for hepatocellular carcinoma. Hydroxyapatite (HAP) was chosen for the carrier material and doxorubicin hydrochloride (DOX) for anticancer agent. DOX-HAP was produced by adsorbing DOX to porous HAP particles of 1375 +/- 125 microns diameter using the freeze drying method. In vitro experiments showed slow release of the drug resulting in the steady release of DOX from HAP for 1 month duration. In healthy white rabbits with DOX-HAP implantation in the liver, serum DOX was not detectable, and DOX release rate was stable at the implanted region after 7, 14, and 21 days. When DOX-HAP (DOX; 100 mg kg-1) was administered to mice with sarcoma 180, an improved survival rate was observed without acute toxicity. We also found that VX2 liver tumour growth on white rabbit was inhibited by implantation of DOX-HAP, without acute toxicity. We hope that DOX-HAP implantation therapy will open up new avenues for the treatment of hepatoma.

Full text

PDF
668

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Audisio R. A., Doci R., Mazzaferro V., Bellegotti L., Tommasini M., Montalto F., Marchianò A., Piva A., DeFazio C., Damascelli B. Hepatic arterial embolization with microencapsulated mitomycin C for unresectable hepatocellular carcinoma in cirrhosis. Cancer. 1990 Jul 15;66(2):228–236. doi: 10.1002/1097-0142(19900715)66:2<228::aid-cncr2820660206>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  2. BIERMAN H. R., BYRON R. L., Jr, MILLER E. R., SHIMKIN M. B. Effects of intra-arterial administration of nitrogen mustard. Am J Med. 1950 Apr;8(4):535–535. doi: 10.1016/0002-9343(50)90263-4. [DOI] [PubMed] [Google Scholar]
  3. Doppman J. L., Di Chiro G., Ommaya A. Obliteration of spinal-cord arteriovenous malformation by percutaneous embolisation. Lancet. 1968 Mar 2;1(7540):477–477. doi: 10.1016/s0140-6736(68)92812-2. [DOI] [PubMed] [Google Scholar]
  4. Goldstein H. M., Wallace S., Anderson J. H., Bree R. L., Gianturco C. Transcatheter occlusion of abdominal tumors. Radiology. 1976 Sep;120(3):539–545. doi: 10.1148/120.3.539. [DOI] [PubMed] [Google Scholar]
  5. Gregoriadis G. Targeting of drugs. Nature. 1977 Feb 3;265(5593):407–411. doi: 10.1038/265407a0. [DOI] [PubMed] [Google Scholar]
  6. Hagiwara A., Takahashi T., Lee R., Ueda T., Takeda M., Itoh T. Chemotherapy for carcinomatous peritonitis and pleuritis with MMC-CH, mitomycin C adsorbed on activated carbon particles. Clinical trials. Cancer. 1987 Jan 15;59(2):245–251. doi: 10.1002/1097-0142(19870115)59:2<245::aid-cncr2820590212>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  7. Hashida M., Kato A., Kojima T., Muranishi S., Sezaki H., Tanigawa N., Satomura K., Hikasa Y. Antitumor activity of mitomycin C-dextran conjugate against various murine tumors. Gan. 1981 Apr;72(2):226–234. [PubMed] [Google Scholar]
  8. KLOPP C. T., ALFORD T. C., BATEMAN J., BERRY G. N., WINSHIP T. Fractionated intra-arterial cancer; chemotherapy with methyl bis amine hydrochloride; a preliminary report. Ann Surg. 1950 Oct;132(4):811–832. doi: 10.1097/00000658-195010000-00018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kato T., Nemoto R., Mori H., Kumagai I. Sustained-release properties of microencapsulated mitomycin C with ethylcellulose infused into the renal artery of the dog. Cancer. 1980 Jul 1;46(1):14–21. doi: 10.1002/1097-0142(19800701)46:1<14::aid-cncr2820460103>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  10. Kato T., Tamakawa Y., Unno K. [Chemo-embolization with mitomycin C microcapsules for hepatoma]. Gan To Kagaku Ryoho. 1984 Apr;11(4):798–805. [PubMed] [Google Scholar]
  11. Konno T., Maeda H., Iwai K., Maki S., Tashiro S., Uchida M., Miyauchi Y. Selective targeting of anti-cancer drug and simultaneous image enhancement in solid tumors by arterially administered lipid contrast medium. Cancer. 1984 Dec 1;54(11):2367–2374. doi: 10.1002/1097-0142(19841201)54:11<2367::aid-cncr2820541111>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  12. Konno T., Tashiro S., Maeda H., Iwai K., Ogata K., Mochinaga M., Uemura K., Ishimaru S., Miyauchi Y., Yokoyama I. [Intra-arterial injection of an oily antineoplastic agent in hepatic cancer]. Gan To Kagaku Ryoho. 1983 Feb;10(2 Pt 2):351–357. [PubMed] [Google Scholar]
  13. Nakamura H., Tanaka T., Hori S., Yoshioka H., Kuroda C., Okamura J., Sakurai M. Transcatheter embolization of hepatocellular carcinoma: assessment of efficacy in cases of resection following embolization. Radiology. 1983 May;147(2):401–405. doi: 10.1148/radiology.147.2.6300959. [DOI] [PubMed] [Google Scholar]
  14. Ozawa S., Sugiyama Y., Mitsuhashi J., Inaba M. Kinetic analysis of cell killing effect induced by cytosine arabinoside and cisplatin in relation to cell cycle phase specificity in human colon cancer and Chinese hamster cells. Cancer Res. 1989 Jul 15;49(14):3823–3828. [PubMed] [Google Scholar]
  15. Ozawa S., Sugiyama Y., Mitsuhashi Y., Kobayashi T., Inaba M. Cell killing action of cell cycle phase-non-specific antitumor agents is dependent on concentration--time product. Cancer Chemother Pharmacol. 1988;21(3):185–190. doi: 10.1007/BF00262767. [DOI] [PubMed] [Google Scholar]
  16. SEMPLE J. E. Papillomata of bladder treated with podophyllin; preliminary report. Br Med J. 1948 Jun 26;1(4564):1235–1237. doi: 10.1136/bmj.1.4564.1235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Seki T., Nonaka T., Kubota Y., Mizuno T., Sameshima Y. Ultrasonically guided percutaneous ethanol injection therapy for hepatocellular carcinoma. Am J Gastroenterol. 1989 Nov;84(11):1400–1407. [PubMed] [Google Scholar]
  18. Takahashi T., Mizuno M., Fujita Y., Ueda S., Nishioka B. Increased concentration of anticancer agents in regional lymph nodes by fat emulsions, with special reference to chemotherapy of metastasis. Gan. 1973 Aug;64(4):345–350. [PubMed] [Google Scholar]
  19. Uchida A., Nade S., McCartney E., Ching W. Bone ingrowth into three different porous ceramics implanted into the tibia of rats and rabbits. J Orthop Res. 1985;3(1):65–77. doi: 10.1002/jor.1100030108. [DOI] [PubMed] [Google Scholar]
  20. Widder K. J., Senyei A. E., Ranney D. F. Magnetically responsive microspheres and other carriers for the biophysical targeting of antitumor agents. Adv Pharmacol Chemother. 1979;16:213–271. doi: 10.1016/s1054-3589(08)60246-x. [DOI] [PubMed] [Google Scholar]
  21. Yamada R., Sato M., Kawabata M., Nakatsuka H., Nakamura K., Takashima S. Hepatic artery embolization in 120 patients with unresectable hepatoma. Radiology. 1983 Aug;148(2):397–401. doi: 10.1148/radiology.148.2.6306721. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES