Fig 1.
Histological image of therectal mucosa (longitudinal section).
Rectal crypts with simple columnar epithelium are visible, and the stroma (lamina propria) is seen wrapping around the crypts. Reprinted from http://www.lab.anhb.uwa.edu.au/mb140/ [25].
Fig 2.
Histological image of the rectal crypts (transverse section).
Regular spacing of the crypt openings is seen. Reprinted from http://www.lab.anhb.uwa.edu.au/mb140/ [25].
Fig 3.
Drawing of the crypt geometry in this model.
The figure is in cylindrical coordinate system used for the computations. The enema fluid fills the canal above the crypt.
Table 1.
Parameters in the model.
Fig 4.
Heat map plot of tenofovir concentration distribution.
The region is in the upper portion of a crypt and the adjacent mucosal tissue at 5 minutes post enema insertion. The crypt has a small size (cf. Table 1) and is open to the enema fluid (see text).
Fig 5.
Volume-averaged TFV and TFV-DP concentrations vs. time after enema application in different compartments.
Enema retention times are 5, 10, or 20 minutes (blue, green and red lines). A small sized crypt is contrasted between being open (hatched line) or closed to the luminal enema fluid (see further details in text). Results are also shown for compartmental volume-averaged concentrations vs. time, as computed for the earlier vaginal model for a tenofovir gel[20]; here there is also complete vehicle coating along the canal. Both vehicles initially contain 107 ng/mL (1%) TFV. Note the much lower and slower developing concentrations in the vaginal mucosal tissue. Contrasts in rectal stromal TFV and TFV-DP concentrations for open vs. closed crypts are also evident.
Fig 6.
Volume-averaged TFV concentrations vs. time in different compartments.
The lines indicate small (green lines) vs. large (blue lines) crypt sizes, which are open (hatched lines) or closed (solid lines). Enema retention time is 5 minutes. For closed crypts, size has a small effect. For open crypts, larger size increases concentrations by up to about 20%.
Fig 7.
Volume average TFV concentrations vs. time in the compartments for varying advective flow.
This is contrasted to a closed crypt (solid lines; see text for further details). Enema retention time is 5 minutes, and crypt size is small. Effects of advection on concentrations are relatively small (see text).
Fig 8.
TFV concentration profile versus depth of the stroma.
This is after 5 minutes of enema retention for a small, open crypt. Different times are indicated by different colors (cf. color bar), and the flattening of the concentration profile vs. depth with increasing time is clearly seen.
Fig 9.
Percentage of stromal volume containing prophylactic TFV-DP concentration vs time.
This is termed “percent protected” after 1 minute or 5 minutes of enema retention for a small crypt. See text for specification of “protected.” Contrasts between the shorter and longer retention times, as well as open vs. closed crypt status, are clearly seen.
Fig 10.
Results for TFV concentrations in a simulated biopsy.
The biopsy contains both epithelium and some stromal tissue (see text). Enema retention time is 5 (blue lines), 10 (green lines) or 20 (red lines) min. Crypts are either open (hatched lines) or closed (solid lines). Biopsy thickness is either 1 mm (left y-axis) or 3 mm (right y-axis), and crypt size is small.
Fig 11.
Results for TFV-DP concentrations in a simulated biopsy.
The biopsy contains both epithelium and some stromal tissue (see text). Enema retention time is 5 min (blue lines), 10 (green lines) or 20 (red lines) min. Crypts are either open (hatched lines) or closed (solid lines). Biopsy thickness is either 1 mm (left y-axis) or 3 mm (right y-axis), and crypt size is small.
Fig 12.
Ratios of predicted TFV-DP concentrations in the mucosal stroma to concentrations in simulated biopsies.
The depth of the biopsy is assumed to be either 1mm or 3mm. Enema retention time is 5 min (blue line), 10 min (green lines) or 20 min (red lines). Crypts are open (hatched lines) or closed (solid lines). Notably, values in biopsies overestimate stromal values by about 3X (shallower 1 mm biopsy) to 9X (deeper 3 mm biopsy). Enema retention time and crypt openness have relatively small effects on this ratio.