Non-ionic surfactant vesicles (niosomes) prepared from a non-ionic surfactant, cholesterol and dicetyl phosphate and containing methotrexate (MTX) have been administered to mice. Given intravenously the niosomes prolong the levels of MTX in the blood, large amounts of the drug being taken up by the liver. There was also an increased uptake of MTX into the brain, perhaps due to an effect of the niosome components on the permeability of the blood brain barrier. Absorption of the drug from the gastrointestinal tract following oral ingestion, appeared to be increased at some doses; most of the entrapped MTX was taken up by the liver, but uptake of MTX into the brain was also increased. The metabolic profile of the drug is altered by the niosomes which appear to prevent the rapid formation of 7-hydroxy methotrexate.

Adriamycin-loaded bovine albumin microspheres have been prepared by a technique that allows preparation and administration to animals on the same day. Criteria adopted for injection were that microspheres should be stable and of a size such as to become trapped in capillary beds. These conditions were fulfilled by preparing microspheres using glutaraldehyde concentrations greater than 0.5 per cent and the appropriate combination of stirring speed and continuous phase viscosity. After systemic administration rats were sacrificed at intervals and major visceral organs examined for entrapped microspheres and serum for released drug. Microspheres sieved out in the first capillary bed encountered, the lung, then following biodegradation they disappeared at a rate dependent on the amount of cross-linking agent used in their preparation. In contrast to bolus injection, serum drug levels after microsphere administration indicated an initial rapid release followed by a more protracted phase lasting at least 24 h. This latter observation is consistent with drug release during biodegradation of carrier.

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.

No abstract