STUDY DESIGN:
Poly(FAD:SA) was loaded with different chemotherapeutic drugs and its in vitro and in vivo drug release and tissue penetration characteristics were studied. The biocompatibility and toxicity of the
polymer-
drug combination were determined. The effectiveness of the
drug-
polymer was evaluated against three different human SCCs (larynx O11, pharynx FADU, and floor of mouth UM- SCC1) cultured in vitro and in nude mice carrying human SCC xenografts.
METHODS: The in vitro drug release pharmacokinetics of the drugs were performed using atomic absorption spectrometry for
cisplatin and high-pressure liquid chromatography for the
5-FU, MTX, and
paclitaxel studies. In vitro
tumor cytotoxicity was assessed by growth assay. In vivo cytotoxicity was assessed by growth rate inhibition in a nude mouse model.
RESULTS: All four
chemotherapy drugs demonstrated a continuous release that followed first-order kinetics from the
polymer. More than 95% of the MTX and
5-FU, 70% of the
cisplatin, and 20% of the
paclitaxel was released within the 10 days of the assay.
Tumor cytotoxicity revealed that the
polymer was very effective against the human SCCs O11, FADU, and UM- SCC1 in vitro. When a small amount of
polymer (1-2 g) was added to the cell culture and left for 7 days, 96.6% of the UM-SCC1 cells, 86.9% of the FADU cells, and 94.6% of the O11 cells were killed. When the culture medium was then changed every 2 days to remove the effect of nutrient depletion or chemicals released by the degrading
polymer, 74% of the UM-SCC1 cells, 94.5% of the FADU cells, and 66.1% of the O11 cells were killed at 7 days. The
tumor animal model was the nude mouse carrying human floor of mouth SCC xenografts. Different amounts of
cisplatin were incorporated into the
polymers (5% and 7%
drug/
polymer at a weight/weight [wt/wt] load). Thirty-five days after implantation of the
polymer in nude mice, the mean treated
tumor size was 65.5% of controls in the 5% group and 31.8% in the 7% group. Seventy days after implantation the mean treated
tumor size was 41.4% of controls in the 5% group and 38.1% in the 7% group, indicating a statistically significant delay of
tumor growth compared with controls or with intraperitoneally injected
cisplatin. The blank
polymer was well tolerated by the mouse and had no effect on
tumor growth.
CONCLUSIONS: