Liposome-Entrapped Diethylstilbestrol Effect on Prostate Gland and Plasma Testosterone Levels in Rats

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Abstract
The effects of liposome-encapsulated diethylstilbestrol (DES) on the size of the ventral prostate gland and total testosterone levels in rats were studied. DES was encapsulated in phosphatidylcholine-cholesterol-stearylamine-.alpha.-tocopherol containing multilamellar liposomes in a molar ratio of 4:5:1:0.01. The liposome suspension or free DES plus blank liposomes were administered s.c. on days 1, 3, and 5 at a dose of 400, 87, or 12 .mu.g/kg. Plasma testosterone values showed a decrease with dose for animals treated with either entrapped DES or free DES. Prostate gland weight/g animal and prostatic protein mg/g animal on day 7 were significantly decreased in the treated animals compared to those in controls dosed with DES plus buffer containing liposomes. There was a body weight loss for the high dose DES-encapsulated animals and for high and medium dose DES plus blank liposome-treated and blank liposome-treated animals over the treatment period, although only the DES-encapsulated group value was statistically significant (P < 0.05). Animals at the other doses did not lose weight, but exhibited weight gains which were less than those observed for sham-injected animals. Rats that received 7 .mu.g/kg liposome-entrapped DES for 4 wk had significantly lower prostate gland weights, prostatic protein levels, and testosterone levels than control animals receiving the same regimen of free DES plus blank liposomes. Liposome-entrapped DES apparently was more effective in decreasing the size of the prostate gland and the desired therapeutic end point (prostate ablation) may be attained with a lower dose of DES, which would decrease the risk of weight loss in the experimental animals. The results are discussed in reference to human prostate malignancy treatment with DES.