Pharmaceutical Development of 5-Fluorouracil-Eluting Stents for the Potential Treatment of Gastrointestinal Cancers and Related Obstructions

Figures & data

Figure 1 Fabricated 5FU-loaded gastrointestinal nitinol stents: (A) Si-PU_FU stent (single-layer, base-coated only) and (B) Si-PU_FU-PEVA stent (double-layer, both base- and top-coated); (C) Ba-PU_FU stent (single-layer, base-coated only) and (D) Ba-PU_FU-PEVA stent (double-layer, both base- and top-coated).

Table 1 Theoretical and Experimental Drug Loading Content for Dip-Coated Nitinol Stents (n = 6)

Sample	Weight (mg)	Theoretical 5FU Content (µg)	Experimental 5FU Content (µg)^a	Recovery Yield (%)^b
Si-PUFU stent pieces	14.93 ± 0.38	392.2 ± 10.1	384.9 ± 16.4	98.10 ± 1.81
Ba-PUFU stent pieces	9.85 ± 0.67	201.0 ± 13.7	201.2 ± 14.7	100.2 ± 5.17

Notes:^aAll experimental amounts of 5FU were measured by HPLC; ^bRecovery yield (%) was calculated from the ratio of experimental to theoretical 5FU content; All values are expressed as mean ± SD.

Figure 2 In vitro release profile of 5-fluorouracil (5-FU) from (A) Si-PU_FU-PEVA stents over 161 days and (B) Ba-PU_FU-PEVA stents over 30 days in phosphate buffer saline (10 mM, pH 7.4). Data represents n = 3, mean ± standard deviation.

Figure 3 Amount of N,N-dimethylformamide (DMF) detected (by HPLC) per day over seven successive days after in vitro release from the Si-PU_FU-PEVA or Ba-PU_FU-PEVA stents in phosphate buffered saline (10 mM, pH 7.4). Three asterisks (***) reflect DMF amount below the HPLC method quantitation limit of 5 ppm. All values represent mean (n = 3) ± standard deviation.

Figure 4 In vitro percentage cumulative 5-fluorouracil (5-FU) release curves from (A) Si-PU_FU-PEVA stents over 14 days and (B) Ba-PU_FU-PEVA stents over 13 days in phosphate buffered saline (10 mM, pH 7.4, 37 °C). Data for control (non-irradiated) and gamma-irradiated stents (n = 2 for all data points, mean ± standard deviation).

Figure 5 Cumulative percent of 5-fluorouracil (5-FU) released in vitro from the representative control and accelerated stability (40 °C and 75% relative humidity) test of the (A) Si-PU_FU-PEVA and (B) Ba-PU_FU-PEVA stents. Data from 3-month stability samples (n = 3 ± standard deviation). For drug release profiles to be similar, difference factor (f1) and similarity factor (f2) need to be ≤ 15 and ≥ 50 (50 to 100), respectively.