Intra uterine estriol delivery systems in baboons release rates in vivo and in vitro and effect on the reproductive cycle
Dmowski, W.P.; Auletta, F.; Scommegna, A.
Contraceptive Delivery Systems 2(2): 177-188
1981
ISSN/ISBN: 0143-6112 Document Number: 438657
Estriol-containing cylindrical capsules were prepared from biocompatible polymer Estane 5714. The capsules were targeted for specific 0-order release rates on the basis of membrane permeability studies. The actual release rates of estriol, as measured in vitro, corresponded closely, after the initial burst effect, to the target release rates. The in vivo release rates were determined using similar capsules filled with radiolabeled estriol. For this purpose, the capsules were inserted into the uteri of mature baboons for 60 wk. During that period, radioactivity was measured in the plasma 3 times a week and in 24 h urine at weekly intervals. Following removal of the labeled devices, the content of residual estriol was determined and in vivo release rates were calculated. Both in vivo and in vitro release rates were similar. The effect of intrauterine estriol on the baboon reproductive cycle was evaluated using estriol delivery systems made of a different biocompatible polymer. These devices were releasing in excess of 12.5 .mu.g/24 h of estriol. The reproductive cycles of 3 baboons were monitored using plasma estradiol and progesterone determinations 3 times a week and endometrial biopsies every 2 wk. Simultaneously, sex skin changes were recorded and observations for menstrual bleeding were performed. Plasma estriol was also determined 3 times a week. There were no alterations in reproductive cycles following insertion of estriol-releasing devices. Three cycles before and 4 cycles after insertion of the device were regular and ovulatory acccording to endocrine and histologic criteria. Also, there was no change in plasma estriol levels which remained close to the sensitivity range of the assay. Intrauterine estriol does not interfere with the reproductive cycle in the baboon. The actual in vivo release rates correspond closely to those determined in vitro.