Factors that influence the penetration of methotrexate through solid tissue.

Abstract:

:Limited penetration of anticancer drugs through tumour tissue is an important factor that may limit therapeutic effects against solid tumours. Here we report studies of the penetration of radiolabelled methotrexate through multicellular layers (MCL) of murine EMT-6 and human MCF-7 cells grown on semiporous teflon membranes. The penetration of methotrexate was only about 25% of that through the teflon membrane alone after 6 hr. This was true for all methotrexate concentrations examined from 10 microM to 3 mM. The presence of folic acid at concentrations above 0.1 mM and of acidic conditions decreased the uptake of methotrexate into single cells and enhanced tissue penetration. Hypoxic conditions and the presence of folinic acid (leucovorin) had no effect on penetration or uptake of methotrexate. Our data provide evidence that tissue penetration of methotrexate is through the extracellular space, that its distribution in solid tissue may be limited and that it may be possible to improve its tissue penetration.

journal_name

Int J Cancer

authors

Cowan DS,Tannock IF

doi

10.1002/1097-0215(20010101)91:1<120::aid-ijc1021>3

keywords:

subject

Has Abstract

pub_date

2001-01-01 00:00:00

pages

120-5

issue

1

eissn

0020-7136

issn

1097-0215

pii

10.1002/1097-0215(20010101)91:1<120::AID-IJC1021>3

journal_volume

91

pub_type

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