Abstract
The objective of this research was to assess ability of biodegradable implantable 5-Fluorouracil dosage forms, to maximize the regional exposure of the drug while limiting its systemic toxicity in rats with induced liver cancer. Liver cancer was successfully induced in male Wistar rats using a selected protocol followed by surgical implantation of prepared 5-FU biodegradable implant. Rats were sacrificed at time intervals and the pooled blood used to perform the different tests and the implant was retrieved, and analyzed to calculate the amount of drug left in implant. The amount of 5-FU in blood was quantified using high pressure liquid chromatography (HPLC). Gross examination of rat liver, calculation of liver to body weight percentage, and complete blood picture analysis were also performed. Liver biopsies were examined to assess signs of liver necrosis. Localized necrotic areas were noted in rat liver biopsies after 5 days with a perimeter of 0.3 to 0.6 cm around the implants indicating the localized 5-FU therapeutic effect. Sustained drug release was detected in rats for about 2 months and the amount of 5-FU released from implant into the systemic circulation was found to represent less than 13%. PLA coated injection molded implants loaded with 5-FU could present a promising dosage form for liver cancer treatment.
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