Abstract
A synthetic nonapeptide agonist of luteinizing hormone-releasing hormone (LH-RH) des-Gly10-[D-Leu6]-LH-RH ethylamide, was entrapped in a nonbiodegradable copolymer of hydrophobia diethylene glycol dimethacrylate and hydrophilic polyethylene glycol #600 dimethacrylate having a sandwich-type structure prepared by radiation-induced polymerization. The two types of controlled release formulations prepared in this study have average release rates of 7 and 320 μg/day in the in vivo experiments. In this case, the controlled release formulations implanted subcutaneously in the backs of male Wistar rats were maintained over a period of 10 weeks. Serum drug levels were found to be 2.6 and 30 ng ml−1 respectively and were constant throughout the experimental period. The serum testosterone level and serum LH level were significantly reduced to castrated values at 2 weeks after implantation. At the same time, the ventral prostates, seminal vesicles, and dorsolateral prostates also showed a considerable decrease in weight. These data show excellent therapeutic potential of LH-RH agonist in controlled release formulations.
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M. Yoshida, M. Asano, I. Kaetsu, K. Nakai, H. Yamanaka, T. Suzuki, K. Shida, and K. Suzuki, Biomaterials, 4, 33 (1983).
M. Yoshida, M. Asano, I. Kaetsu, K. Nakai, H. Yamanaka, K. Shida, and K. Suzuki, Polym. J., 14, 941 (1982).
K. Nakai, H. Yamanaka, M. Uehara, H. Yuasa, E. Takahashi, T. Suzuki, K. Shida, M. Yoshida, and I. Kaetsu, Horumon to Rinsho, 30, 1119 (1982).
T. Tamura, M. Go, D. Wada, K. Kunitomo, M. Takehara, M. Ando, M. Udaka, H. Yoshikawa, N. Komi, I. Kaetsu, and M. Yoshida, Gan to Kagakuryoho, 10, 41 (1983).
H. Yamanaka, K. Nakai, K. Shida, A. Shiraishi, M. Yoshida, and I. Kaetsu, J. Steroid Biochem., 19, 12s (1983).
J. P. Gearhart, R. Witherington, and C. H. Coleman, Urology, 17, 44 (1981).
S. K. Chandrasekaran, R. Capozza, and P. S. L. Wong, J. Membr. Sci., 3, 271 (1978).
M. Yoshida, M. Asano, I. Kaetsu, H. Yamanaka, K. Nakai, H. Yuasa, and K. Shida, Abstracts of 103rd Meeting of the Pharmaceutical Society of Japan, Tokyo, 1983, p 160.
T. Makino and H. Yamanaka, Kitakanto Igaku, 33, 321 (1983).
M. Fujino, T. Fukuda, S. Shinagawa, S. Kobayashi, I. Yamazaki, R. Nakayama, Biochem. Biophys. Res. Commun., 60, 406 (1974).
C. Auclair, P. A. Kelly, D. H. Coy, A. V. Schally, and F. Labrie, Endocrinology, 101, 1890 (1977).
H. Okada, I. Yamazaki, Y. Sakurai, T. Yashiki, T. Shimamoto, and H. Miya, J. Pharm. Dyn., 6, 512 (1983).
I. Yamazaki and H. Okada, Endocrinol. Japon., 27, 593 (1980).
T. Makino, Foria Endocrinol. Japon., 49, 629 (1973).
K. Wakabayashi, Endocrinol. Japon., 24, 473 (1973).
N. Faure, F. Labrie, A. Lemay, A. Belanger, Y. Gourdeau, B. Laroche, and G. Robert, Fertility and Sterility, 37, 416 (1982).
B. J. A. Furr, B. E. Valcaccia, M. Sullivan, and F. G. Hutchinson, Abstracts of 74th Annual Meeting of the American Association for Cancer Research, San Diego, 1983, p 185.
M. Yoshida, M. Asano, I. Kaetsu, H. Yamanaka, K. Nakai, H. Yuasa, K. Shida, K. Wakabayashi, and K. Suzuki, Polym. Prepr., Jpn., 32, 1935 (1983).
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Yoshida, M., Asano, M., Kaetsu, I. et al. Pharmacological Response in Male Rats with Controlled Release Formulations of Luteinizing Hormone-Releasing Hormone Agonist. Polym J 18, 287–296 (1986). https://doi.org/10.1295/polymj.18.287
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DOI: https://doi.org/10.1295/polymj.18.287