Effect of intra-vas deferens injection of gossypol-polylactic acid on fertility and spermatogenesis in rats.

In order to reduce gossypol's side effects, we applied a controlled drug release system. In this system gossypol is carried on a polymer of polylactic acid which controls drug release and can also be injected into the vas deferens so that the drug can act continuously and directly on spermatogenesis. We used a single dose of gossypol-polylactic acid (0.35 mg/0.1 ml for each vas deferens) which is only 0.2% of the usual antifertility dose. Fertility tests showed that male rats became infertile 4 weeks after intravasal injection of gossypol-polylactic acid. Gross and microscopic findings in the heart, liver, kidneys and lungs revealed no evidence of pathologic change. Treated rats gained body weight as fast as did the controls. The majority of spermatozoa showed breakage of the axial fibers, indicating that gossypol had diffused into the testes. The fertility of the treated rats recovered four to eight months after treatment. Gossypol-polylactic acid injected into the vas deferens exhibited a low degree of toxic side effects and a high antifertility activity, and is therefore an important approach to decreasing the side effects while enhancing the antifertility specificity of gossypol.