SUN-203 Histopathological Evaluation of Prostatic Tissue upon Long Term Sustained Delivery of Diazole

The objective of this study was to quantitatively evaluate the possible morphological alterations that occur in the columnar epithelial cells of the prostate peripheral zone during early development of benign prostatic hyperplasia (BPH). In this study, BPH was induced by the continuous and sustained delivery of Danazol (androgen analog) through tricalcium phosphate-lysine (TCPL) drug delivery devices (OD: 0.8 mm, ID: 0.4 mm and density: 1.98 ± 0.53 gm/cm(3)). A total of 24 adult male rats (BW: 280-320 gm) were randomly divided into three equal groups. Group 1 served as an intact control and Groups 2-3 were implanted with TCPL devices designed to deliver continuous physiologic (3-5 ng/ml) doses of Danazol (DZ) following standard laboratory surgical methods. Upon completion of the study (12 weeks), the resected prostate were subjected to histopathological evaluation. Specifically, the columnar epithelial cells were targeted for morphometric analysis. The means number of cells per high power field, cell length, cell area; nuclear area and nuclear to cytoplasmic ratio (N/C) were measured using digital image analysis software technique. The results of this study revealed that: (i) the number of cells per high power field were unchanged with DZ exposure (log 1.22 ± 0.32) compared to controls (log 1.22 ± 0.26); (ii) the cell length was significantly (P < 0.05) decreased with upon DZ exposure (0.9 ± 0.03 µm) compared to controls (1.32 ± 0.51 µm), (iii) the cellular area was decreased with DZ (1.02 ± 0.056 µm( 2)) compared to controls (1.59 ± 0.102 µm( 2) , and (iv) the N/C ratio was increased (0.279 ± 0.032 um) compared to controls (0.188 ± 0.021 µm). The results of this study suggest that sustained delivery of DZ by TCPL modality resulted in a remarkable alteration during early development of BPH. These finding may alert a pre-dysplastic outcomes from sustained delivery of DZ.