The Role of Sustained Release of Testosterone from TCP and ZCAP Delivery Systems in Adult Rodents

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 524-553-Male Reproductive Endocrinology
Bench to Bedside
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-534
Hamed A Benghuzzi*1 and Michelle Tucci2
1Univ of MS Med Ctr, Jackson, MS, 2Univ of Mississippi Med Ctr, Jackson, MS
This study was designed to investigate the role of sustained delivery of testosterone (TE) on fertility regulation using adult male rats as a model. The microcrystals of tricalcium phosphate (TCP) and zinc calcium phosphate (ZCAP) were prepared by following standard laboratory techniques. The calcined materials of TCP and ZCAP were compressed into cylindrical forms (ID =0.04 cm, OD =0.08, Wt = 1 gr, Compression Load 2900 Kg) and sintered at 1400 oC for 36 hours. Experimental TCP and ZCAP capsules were loaded with 50 mg TE crystal (75 um Particle size). The final density of the delivery capsules was 1.78 ± 0.05 gm/cm3 and surface area of 3.90±0.46 cm3. A total of 128 Sprague Dawley rats weighing 280-320 gm were divided randomly into four groups of 32 rats each. All animals' in-groups II-IV were castrated following standard surgical procedure.  Each rat in groups I served as intact control, group II animals were sham (A) operated (empty implants).    Rats in groups III and IV were implanted with ZCAP-TE and TCP-TE.    The data collected were analyzed by analysis of variance at p>0.05. The sterilized (gas) ceramics were inserted under the skin (axillary region) using standard aseptic surgical techniques.  Eight rats were sacrificed from each group at the end of 4, 8,12  and 16 weeks. Vital and reproductive organs were collected and analyzed by histomorphometry.  Collection of Blood:  blood was collected weekly from each rat and TE levels were measured.  Data  demonstrated that TCP and ZCAP delivery systems were capable of releasing TE at sustained levels for 16 weeks. The rate of TE release from ZCAP and TCP capsules were 3.45 ± 0.54 and 2.40 ± 0.22, respectively.   Gross, radiographic and histological examinations did not show any untoward reactions during the entire investigation.  Results showed that the passage of TE through TCP and ZCAP capsules started within 4 days after implantation. Screening of the vital organs showed no cellular injury in all groups compared to the controls. The prostatic tissue obtained from rats implanted with ZCAP-TE showed evidence of hyperplasia which varied somewhat from one area of the gland to another, but generally, there was occasional glandular folds and an increase in the number and size of the epithelial cells. Meanwhile, cross-sections of prostate obtained from rats implanted with TCP-TE were characterized by an essentially normal histological appearance of the gland. In conclusion the data suggest: (i) biodegradability of TCP and ZCAP delivery systems serve to enhance the rate of TE release over time by increasing the size of the micro/macropores in the device, (ii) the use of TCP-TE devices reduces the rate of resorbability of the ceramic and maintains a smaller pore size resulting in lower release profiles thereby lengthens the interval of  TE release from the implant,  and (iii) sustained delivery of TE from TCP and ZCAP delivery systems provided an ideal means to regulate fertility in males.

Nothing to Disclose: HAB, MT

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