The effect of the substitution level of some dextran-methotrexate conjugates on their antitumor activity in experimental cancer models.
نویسندگان
چکیده
Methotrexate (MTX) is widely used in the treatment of a number of oncological and hematological diseases. Due to its known limitations, MTX is often conjugated with different carriers to obtain amended forms of the drug. In this study, the potential influence of the substitution level (loading ratio) of the dextran T10- and T40-based MTX conjugates (D-MTX) on their properties were investigated in vitro and in vivo. The clear dependence of the in vitro antiproliferative effect on the substitution level was established only in the case of the dextran T10-based preparations (T10-MTX conjugates). Conjugates with the higher substitution level had the lower antiproliferative effect. For the dextran T40-based (T40-MTX conjugates) set no similar relationship was observed in the tested range of substitution levels, nor was any dependence observed between the biological properties of the D-MTX preparations in vivo and their substitution levels. However, the difference between the two conjugates was well pronounced in a multiple-dose schedule, when the advantage of T40-MTX over T10-MTX was cumulative during the prolonged course of administration.
منابع مشابه
Antitumor properties and toxicity of dextran-methotrexate conjugates are dependent on the molecular weight of the carrier.
Methotrexate (MTX) is widely utilized in the clinical treatment of many forms of cancer. However, the drug has a short plasma half-life and causes toxic effects on normal proliferating cells. Conjugation with carriers is a possible way to alter these disadvantageous pharmacokinetics. Our aim was to synthesize dextran-MTX (D-MTX) conjugates, using carriers with molecular weights (Mw) ranging fro...
متن کاملEvaluation of the Anticancer Effect of Xanthium Strumarium Root Extract on Human Epithelial Ovarian Cancer Cells Using 1H NMR-Based Metabolomics
Epithelial Ovarian cancer is the leading cause of cancer mortality among women all over the world. As chemotherapeutics has many side effects, researchers have focused on the potential use of medicinal plants as natural antitumor agents. Xanthium strumarium studied in this work as an herbal anticancer agent. This study aimed to evaluate the antitumor effect and metabolic alterations ca...
متن کاملEVALUATION OF ANTI-CANCER ACTIVITY OF COVALENTLY CONJUGATED METHOTREXATE TO POLYAMIDOAMINE GENERATION 4 DENDRIMER ON MCF-7 CANCER CELLS: AN EXPERIMENTAL STUDY
Background & Aims: Poly (amidoamine) dendrimer (PAMAM) is highly macromolecular at nanosize with widely active amine groups on the surface that allows it to attach to the anti-cancer drugs such as Methotrexate (MTX). This study aimed to synthesize and characterize PAMAM-MTX (dendrimer-MTX) complex, then to evaluate the cytotoxic effect of the synthesized complex on MCF-7 cancer cells. Material...
متن کاملCovalent coupling of methotrexate to dextran enhances the penetration of cytotoxicity into a tissue-like matrix.
For antitumor agents introduced directly into the intracranial space, the extent of penetration into tissue, and hence the effectiveness of therapy, depends on the rate of drug elimination from the tissue. To test the hypothesis that slowly eliminated agents would penetrate further through tissues, methotrexate (MTX)-dextran conjugates were produced by covalently linking MTX to dextran through ...
متن کاملEVALUATION OF HMGA2 AND SMARCA5 GENES EXPRESSION IN 4T1 CELLS EXPOSED TO METHOTREXATE: BIOINFORMATIC AND EXPERIMENTAL STUDY
Background & Aims: Breast cancer is a threatening disease in females and is the second common cancer among women after lung cancer. The aim of this research is to bioinformatically and experimentally evaluate the effect of methotrexate (MTX) on the expression of HMGA2 and SMARCA5 genes in the MTX treated 4T1 cancer cell line. Materials & Methods: To perform this study, initially microarray dat...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Anticancer research
دوره 26 3A شماره
صفحات -
تاریخ انتشار 2006