Controlled release of therapeutic agents: slow delivery and cell encapsulation

Some of the most promising systems for the controlled release of bioactive agents, i.e., peptides or hormones. involve the encapsulation or entrapment of hormones or peptides in biocompatible polymeric devices that enable the ir continuous release over prolonged periods. In urology, two major patholo gic conditions. androgen deficiency and prostate cancer, currently benefit from treatments based on controlled delivery. Leuprolide acetate depot (Lup ron-depot) was one of the first controlled-delivery systems used for the tr eatment of prostate cancer. Clinical studies indicate that patients with pr ostate cancer who undergo therapy with leuprolide acetate depot can benefit from this treatment. Currently available androgen-replacement therapies in clude the oral administration of testosterone tablets or capsules. depot in jections, sublingual treatment, and skin patches. However. side effects suc h as metabolic inactivation of testosterone on oral administration: fluctua tions in levels of the hormone: and burning, rash, and skin necrosis during the use of skill patches may occur. These side effects may be avoided thro ugh the application of encapsulated Leydig cells, which produce testosteron e. Studies in our laboratory have shown that Leydig cells encapsulated in a lginate/poly-L-lysine/alginate microspheres are capable of secreting testos terone in culture and in vivo. Microencapsulated Leydig cells delivered int raperitoneally into castrated rats: maintained a testosterone level of 0.51 ng/ml for more than 3 months without any human chorionic gonadotropin stim ulation. Similar studies are also being conducted in our laboratory on enca psulation of ovarian cells for the secretion of progesterone and estrogen i n culture and in vivo using microencapsulation techniques.