The Effects of Long-Term Sustained Delivery of Dihydrotestosterone by Poly(lactic acid) Impregnated and Noncoated Biodegradable Ceramic Devices in Male Rodents

Abstract

The objectives of this investigation were to evaluate the release of dihydrotestosterone (DHT) from nonimpregnated and poly(lactic acid) (PLA) impregnated ALCAP ceramic reservoirs implanted in male rats, and to study the effects of delivered DHT on the reproductive system of male rats. A total of 120 Sprague-Dawley male albino rats were distributed equally into three groups. Two ALCAP capsules, one nonimpregnated and the other impregnated with PLA, were implanted in each rat in groups I and II. Capsules implanted in group I rats were loaded with 40 mg DHT each. Group II rats were implanted with two empty capsules (sham group), and group III animals served as un implanted controls. Eight rats from each group were euthanized at the end of the one, three, six, nine, and twelve months following the implantation of the ceramics. No significant changes in the weights of vital organs of rats were observed among any of the three different groups. Vas deferens and epididymal fluid were devoid of normal spermatozoa within three months of implanting the steroid-containing ceramics. Testes weights decreased significantly in the rats implanted with ALCAP ceramics containing DHT and the seminiferous tubules became oligospermic after one month and azoospermic after three months. The data collected in this study suggest that: (1) ALCAP ceramic cap sules are capable of delivering DHT for one year at a sustained manner; (2) DHT delivered by ALCAP capsules can be used effectively to regulate sperma togenesis in rats.

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References

Imperato-McGinley, J. , R. Peterson , T. Gautier and E. Sturla. 1979. " Male Pseudohermaphroditism Secondary to 5-Alpha-Reductase: A Model for the Role of Androgens in Both the Development of the Male Phenotype and the Evolution of Male Gender Identity ," J. Steroid Biochemical, 11:637-646.

Wilson, J. and I. Lasnitzki. 1971. "Dihydrotestosterone Formation in Fetal Tissues of the Rabbit and Rat," Endocrinology, 89(3):659-668.

Bruchovsky, N. and J. Wilson. 1968. "The Conversion of Testosterone to 5x-Androstane-17B-ol-3-One by Rat Prostate in vivo and in vitro," J. Biol. Chem., 243:2012-2021.

Gloyna, R. and J. Wilson. 1969. "A Comparative Study of the Conversion of Testosterone 17B-Hydroxy-5x-Androstant-3-One (DHT) by Prostate and Epididymis ," J. Clin. Endocrinol., 29:970-983.

Bajpai, P.K. and H.A. Benghuzzi. 1988. "Ceramic System for Long-Term Delivery of Chemicals and Biologicals," J. of Biomed. Mat. Res., 22:1245-1266.

Benghuzzi, H.A. , P.K. Bajpai , D. Strong , P. Delli and L. Loose. 1989. "Resorbable and Biodegradable Ceramics as Drug Delivery Systems," Digest of Papers, Eighth Southern Biomedical Engineering Conference, Richmond, VA , 1989. W. A. Krause, ed. Washington:McGregor and Werner, pp. 58-61.

Benghuzzi, H.A. and P.K. Bajpai. 1987. "The Effects of ALCAP Mixed Particle Sizes on Density and Delivery of Proteins in vitro," Proc of the 13th Annual Northeast Bioengineering Conference, Philadelphia, PA, March 12-13, 1987, pp. 566-569.

Benghuzzi, H.A. and P.K. Bajpai. 1988. "Effects of Poly(lactic acid) Impregnation and Compression Load on the Delivery of Proteins, Steroids, and Amino Acids from ALCAP Ceramic Capsules," Proc of the 17th Southern Biomedical Engineering Conference, Greenville, SC. D. Moyle, ed., p. 36.

Benghuzzi, H.A. and P.K. Bajpai. 1987. "The Delivery of Progesterone, Estradiol and Androstanedione Combinations from ALCAP Ceramic Capsules," Proc. of the Sixth Southern Biomedical Engineering Conference , Dallas, TX, Oct. 23-24, 1987, pp. 134-137.

10.

Benghuzzi, H.A. and P.K. Bajpai. 1989. "A Ceramic System for Delivering Mixtures of Steroids," Proc. of the 15th Annual Northeast Bioengineering Conference, Boston, MA, 1989, S. Buns , ed., p. 61.

11.

Benghuzzi, H.A. and P.K. Bajpai. 1989. "Effects of Delivering Different Amounts of Dihydrotestosterone by Ceramic Implants on the Reproductive System of Male Rats," Proc of the 26th Annual Rocky Mountain Bioeng. Symp. and 26th International ISA Biomed. Science Instrumentation Symposium , Ames, Iowa, 1989, D. Carlson, ed., pp. 179-189.

12.

Feigelson, M. 1986. "Suppression of Testicular Maturation and Fertility Following Androgen Administration to Neonatal Male Rats," Biol. of Reprod., 35:1321-1332.

13.

Fitzpatrick, F. and B. Greenstein. 1987. "Effects of Various Steroids on the Thymus, Spleen, Ventral Prostate and Seminal Vesicles in Old Orchidectomized Rats," J. Endocr., 113:51-55.

14.

Wilson, J. and R. Gloyna. 1970. "The Intranuclear Metabolism of Testosterone in the Accessory Organs of Reproduction,' Recent Prog. Horm. Res., pp. 309-313.

15.

Imperato-McGinley, J. , L. Guerrezo , T. Gautier and R. Peterson. 1974. "Steroid 5-Alpha-Reductase Deficiency in Man: An Inherited Form of Male Pseudohermaphroditism," Science, 186:1213-1216.

16.

Peterson, R. , J. Imperato-McGinley , T. Gautier and E. Sturla. 1977. " Male Pseudohermaphroditism Due to Steroid 5-Alpha-Reductase Deficiency," Am. J. Med, 62:170-173.

17.

Djoseland, O. , C. Hastings and V. Hansson. 1986. " Androgen Metabolism by Rat Epididymis 5. Metabolic Conversion and Nuclear Binding after Injection of 5x-Androstane-3x, 17b-Diol in vivo," Steroids, 28:585-596.

18.

Buhl, A. and J. Cornete 1982. "Hypophysectomized Male Rats Treated with Polydimethylsiloxane Capsules Containing Testosterone: Effects on Spermatogenesis, Fertility and Reproductive Tract Concentration of Androgens," Biol. of Reprod. , 27:183-188.

19.

Geller, J. , J. Albert , D. Lopez , S. Geller and G. Niwayama. 1976. "Comparison of Androgen Metabolites in Benign Prostatic Hypertrophy (BPH) and Normal Prostate;" J. Clin. Endocrinol. Metab., 43:686-689.