Immunospecific Albumin Microspheres as delivery system for Cisplatin and 5-Fluorouracil for the treatment of ovarian adenocarcinoma

Abstract

The dose of chemotherapeutic agents is considered to be a limiting factor in the treatment of cancer. An ideal chemotherapeutic strategy could be to deliver a high concentration of drug that would be released in sustained small amounts from targeted microspheres to effectively kill only tumour cells but yet reduce toxicity to normal tissue. This theory was tested in vitro before it was evaluated in a rodent model. We showed that small amounts of drugs were released in a sustained fashion over a two week period. Cells of a rodent ovarian carcinoma cell line were exposed to cisplatin and 5-fluorouracil, either as free drug or encapsulated in albumin microspheres that were either conjugated to monoclonal antibodies or not. Clonogenic and cell survival growth curve assays, as well as micronucleus assays, were used to determine the feasilbility of employing targeted immunomicrospheres as a treatment regimen for ovarian cancer. In cell survival growth curve assays, cell survival was reduced to 1.2% of the control and in clonogenic assays it was reduced to 7.87% when cells were treated with drug-containing immunomicrospheres. 3.2-fold more micronuclei were found in those cells that had been exposed to the drugs in immunomicrospheres than in those subjected to untargeted microspheres. Thus, these results indicate that immunomicrospheres are more effective in delivering cisplatin and 5-fluorouracil