Pharmacokinetics of methotrexate–albumin conjugates in tumor-bearing rats

  title={Pharmacokinetics of methotrexate–albumin conjugates in tumor-bearing rats},
  author={Gerd Stehle and Andreas Wunder and Hannsjörg Sinn and Hans Hermann Schrenk and Sandra Schiitt and Eva Frei and Gernot Hartung and W Maier-borst and Dieter L. Heene},
  journal={Anti-Cancer Drugs},
Linking chemotherapeutic drugs to a macromolecular carrier system may enhance tumor targeting, reduce toxicity and overcome drug resistance mechanisms. As an elementary model to evaluate the pharmacological properties of macromolecular drug carrier systems we chose rat serum albumin (RSA) for carrier and methotrexate (MTX) as antineoplastic drug. The conjugation procedure yielded conjugates with an approximate 1:1 molar loading rate (MTX(1)-RSA). In the first part of the study a residualizing… Expand
Antitumor activity of methotrexate‐albumin conjugates in rats bearing a Walker‐256 carcinoma
MTX‐albumin conjugates show therapeutic activity in vivo without toxic side effects and are evaluated for the combination treatment with MTX and MTX‐ albumin, with complete remission in all 20 rats. Expand
Efficacy and tolerability of an aminopterin–albumin conjugate in tumor-bearing rats
In this comparative study, the AMPT–SA conjugate showed high antitumor activity in vivo and a favorable toxicity compared to low-molecular-weight AMPT, which seems to be an effective tool for selective tumor drug targeting. Expand
Pre‐clinical evaluation of a methotrexate–albumin conjugate (MTX‐HSA) in human tumor xenografts in vivo
The improved therapeutic effects seen in 3 xenograft models under MTX‐HSA treatment are promising and might be due to specific accumulation of the compound in solid tumors owing to their enhanced permeability and retention effect. Expand
Albumin-Based Drug Delivery as Novel Therapeutic Approach for Rheumatoid Arthritis1
We reported recently that albumin is a suitable drug carrier for targeted delivery of methotrexate (MTX) to tumors. Due to pathophysiological conditions in neoplastic tissue, high amounts of albuminExpand
Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles.
  • F. Kratz
  • Medicine
  • Journal of controlled release : official journal of the Controlled Release Society
  • 2008
This review gives an account of the different drug delivery systems which make use of albumin as a drug carrier with a focus on those systems that have reached an advanced stage of preclinical evaluation or that have entered clinical trials. Expand
Anticancer carrier-linked prodrugs in clinical trials
This review summarizes the Phase I – III studies that have been performed with drug conjugates that have recently entered clinical trials and includes a methotrexate–albumin conjugate and an albumin-binding doxorubicin prodrug. Expand
Overcoming methotrexate resistance in breast cancer tumour cells by the use of a new cell-penetrating peptide.
Cell-penetrating peptide conjugation of MTX is a new way of increasing delivery, and thereby, the potency of already well-characterized therapeutic molecules into drug resistant tumour cells. Expand
Albumin-coupled methotrexate (MTX-HSA) is a new anti-arthritic drug which acts synergistically to MTX.
The data show that the effectiveness of MTX-HSA in CIA is superior to MTX and that both drugs act synergistically, suggesting that they might be one of the potential target cells of this novel anti-arthritic treatment approach. Expand
Serum proteins as drug carriers of anticancer agents: a review.
This review covers the diagnostic evidence for tumor accumulation of serum proteins and the design, development, and biological evaluation of drug conjugates with transferrin, albumin, and low-density lipoprotein. Expand
Synthesis and biological activity of raltitrexed-carrier conjugates.
Interestingly, it was noticed that the conjugates based on dextran and albumin were more cytotoxic than the free drug in the highest concentrations tested (1000 and 10000 ng/ml). Expand