Investigation of Cytotoxic and Antimicrobial Effects of Polyanhydride-Based Poly[(maleic anhydride)-<i>co</i>-(vinyl Acetate)] Conjugates Combined with Methotrexate and Gemcitabine in Breast Cancer Treatment

Studies aimed at increasing the efficacy of chemotherapeutic drugs and reducing or completely eliminating their side effects are frequently encountered. In our study, we considered methotrexate (MTX), which is in the category of anticarcinogenic and anti-inflammatory drugs, and gemcitabine (GEM), which is used in the treatment of breast, testicular, ovarian, etc. cancers. GEM, which is used in the treatment of breast, testicular, ovarian, etc. cancers, was covalently bonded to maleic anhydride vinyl acetate (MAVA) copolymer, and new polymer-drug conjugates (MAVA-MTX and MAVA-GEM) were obtained to reduce or eliminate the side effects of these drugs and to investigate the cytotoxic and antimicrobial effects of the new conjugates. The conjugation reaction was carried out in the presence of a triethylamine catalyst in dimethylformamide medium at 70 °C. Chemical structure elucidation of the copolymer (MAVA) and conjugates (MAVA-MTX and MAVA-GEM) was carried out by Fourier transform infrared (FTIR) and Nuclear Magnetic Resonance (¹H NMR) spectroscopy. Anticancer activity was determined by the MTT assay in MCF-7 (breast cancer), and L929 (mouse fibroblast) cell lines. The synthesized copolymer and conjugate structures were proved by FTIR and ¹H NMR spectra. It was determined that the conjugates did not form an inhibition zone on the test microorganisms. MIC values were found to be moderately effective compared with reference sources. The anticancer activities of MAVA-MTX and MAVA-GEM conjugates were significantly higher than those of methotrexate and GEM. The higher anticancer activity of the synthesized MAVA-MTX and MAVA-GEM conjugates compared with the drug they contain suggests that they can be a potential drug candidate in the treatment of breast cancer. In addition, the conjugates showed less toxic effect on a healthy L929 cell line at 6 different concentrations compared to free drugs. This can be shown as a significant improvement in reducing one of the most important side effects of the drug, such as toxicity.