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Updated: Aug 17, 2026
Comprehensive Evaluation of the Effectiveness and Safety of Placenta-Targeted Drug Delivery Using Three Complementary Methods
Published on: September 10, 2018
The distribution and elimination of methotrexate in mouse blood and brain after concurrent administration of
Abstract:
This paper describes further exploration of the effect of polysorbate 80 on the absorption, distribution, and elimination of methotrexate (MTX). This study has confirmed the earlier finding that polysorbate 80 could increase the absorption of MTX from the mouse gastrointestinal tract and enhance the drugs uptake into the brain. The experiments reported here suggest that polysorbate 80 has a direct effect on the blood-brain barrier leading to the increased uptake of MTX, which is evident following IV administration. Measurements of MTX excreted in the urine and faeces confirmed the role of polysorbate 80 in facilitating the excretion of MTX into the bile and urine. Polysorbate 80 administered PO did not cause any reduction of plasma volume, thus excluding the possibility that the higher MTX concentrations measured in mice after concurrent administration of polysorbate PO might result from a reduction in blood volume due to osmotic effects. At the doses given, polysorbate 80 appeared not to have a damaging effect on the gastrointestinal mucosa.
Insights
Polysorbate 80 enhances methotrexate (MTX) absorption and brain uptake. This study confirms polysorbate 80 facilitates MTX excretion and does not damage the gastrointestinal tract.
Area of Science:
- Pharmacokinetics
- Drug Delivery
- Toxicology
Background:
- Methotrexate (MTX) is a crucial chemotherapy agent.
- Understanding factors influencing MTX absorption, distribution, and elimination is vital for optimizing treatment.
- Polysorbate 80 is a commonly used excipient with potential pharmacokinetic effects.
Purpose of the Study:
- To further investigate the impact of polysorbate 80 on methotrexate (MTX) pharmacokinetics.
- To elucidate the mechanisms by which polysorbate 80 affects MTX absorption, distribution, and elimination.
- To assess the safety of polysorbate 80 on gastrointestinal mucosa and plasma volume.
Main Methods:
- Animal studies involving oral and intravenous administration of MTX with and without polysorbate 80.
- Measurement of MTX concentrations in plasma, brain, urine, and feces.
- Assessment of gastrointestinal mucosal integrity and plasma volume changes.
Main Results:
- Polysorbate 80 significantly increased MTX absorption from the gastrointestinal tract.
- Enhanced MTX uptake into the brain was observed, suggesting a direct effect on the blood-brain barrier.
- Polysorbate 80 facilitated MTX excretion into bile and urine.
- No reduction in plasma volume or damage to the gastrointestinal mucosa was detected.
Conclusions:
- Polysorbate 80 positively modulates MTX pharmacokinetics, improving absorption and brain penetration.
- The excipient plays a role in enhancing MTX elimination via biliary and urinary routes.
- Polysorbate 80 appears safe for concurrent administration with MTX at tested doses, without adverse effects on GI mucosa or plasma volume.
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