The loading rate determines tumor targeting properties of methotrexate albumin conjugates in rats

  title={The loading rate determines tumor targeting properties of methotrexate albumin conjugates in rats},
  author={Gerd Stehle and Hannsjörg Sinn and Andreas Wunder and Hans Hermann Schrenk and Svenja Sch{\"u}tt and W Maier-borst and Dieter L. Heene},
  journal={Anti-Cancer Drugs},
Albumin dominates the plasma proteins in man. Following our observation that albumin turnover in rodent tumors is markedly increased, we will present evidence that albumin can be employed as an efficient carrier for targeting cytostatic agents like methotrexate (MTX) into tumors. The considerable discrepancy in the molecular weight of MTX (454 Da) and albumin (about 67 000 Da) tempted researchers to load multiple drug molecules on one carrier molecule. It was supposed that the optimal… 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
In Vitro and in Vivo Antitumor Activity of Methotrexate Conjugated to Human Serum Albumin in Human Cancer Cells 1
To avoid systemic toxicity of the cytotoxic drug methotrexate (MTX) and to improve tumor selectivity, MTX was bound to human serum albumin (HSA) as a drug carrier. To understand more about theExpand
In vitro and in vivo antitumor activity of methotrexate conjugated to human serum albumin in human cancer cells.
MTX-HSA is effectively taken up by the cells via albumin receptor- or folate receptor-mediated endocytosis and time-dependently released as an active compound into the cytosol to exert an inhibiting effect on TS and to induce cell cycle alterations. 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
Controlled loading of albumin-drug conjugates ex vivo for enhanced drug delivery and antitumor efficacy.
  • Xinquan Liu, R. Mohanty, +5 authors D. Ghosh
  • Chemistry, Medicine
  • Journal of controlled release : official journal of the Controlled Release Society
  • 2020
Site-specific loading of drug to albumin at 1:1 ratio allowed the conjugate to maintain the native structure of albumin and its intrinsic properties and it has the potential to greatly improve the outcomes of anticancer therapy. Expand
Drug conjugates with albumin and transferrin
Transferrin and albumin are potential macromolecular carriers for improving biodistribution, pharmacokinetic profile and targeting potential of drugs in general. Although the tissue distribution ofExpand
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
Growth inhibition, drug load, and degradation studies of gelatin/methotrexate conjugates.
Conjugates with MTX:gelatin molar ratios ranging from 1:1 to 27:1 were examined for cell growth inhibition, stability, degradation, and methotrexate (MTX) release, finding reduced growth inhibition by high MR conjugates may be due to a hindered enzymatic degradation in the lysosomes. Expand
Albumin and its application in drug delivery
  • D. Sleep
  • Chemistry, Medicine
  • Expert opinion on drug delivery
  • 2015
The FcRn receptor has additional functionality, especially in relation to immunology, antigen presentation and delivery of proteins across mucosal membranes, consequently albumin-based fusions and conjugates may have a future role in oral and pulmonary-based vaccines and drug delivery. Expand