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Transient and controllable opening of the
blood-brain barrier to cytostatic and antibiotic agents by alkylglycerols in
rats
Erdlenbruch B, Jendrossek V, Eibl H, Lakomek M
Kinderklinik, Universitat Gottingen, Robert-Koch-Strasse 40,
37075 Gottingen, Germany.
erdlenbr@med.uni-goettingen.de
The blood-brain barrier hinders progress in the chemotherapy of brain tumors due
to insufficient penetration of anticancer drugs into the brain tissue.
Short-chain alkylglycerols affect the physicochemical properties of biological
membranes.
The enhancement of the blood-brain barrier permeability by intra-arterial
administration of alkylglycerols was investigated in tumor-free and C6
astroglioma bearing rats.
The antineoplastic agents cisplatin and methotrexate and the antibiotics
vancomycin and gentamicin were selectively injected into the right internal
carotid artery in the absence and presence of various alkylmono-, alkyldi-, and
alkyltriglycerols.
In normal rats the intra-arterial administration of the drugs without
alkylglycerols resulted in low drug concentrations in brain tissue.
In the presence of alkylglycerols (0.01-0.3 M) a reversible (within minutes) and
concentration-dependent enrichment of the coinjected agents was found,
preferentially in the ipsilateral hemisphere.
The extent of drug accumulation in the brain was modified by changes in the
chemical structure of the alkylglycerols.
The effect increased with the chain length of the alkyl group, decreased with
the number of glycerols, and varied from 2- to more than 230-fold compared to
controls.
In rats with C6 tumors 1-O-pentylglycerol increased the delivery of methotrexate
18-fold in the tumor, 28-fold in the surrounding brain, 18-fold in the
contralateral brain, and 19-fold in the cerebellum compared to controls with
methotrexate in the absence of pentylglycerol.
In conclusion, the intra-arterial administration of alkylglycerols represents a
novel and well controllable method for enhanced drug delivery to the brain and
to brain tumors.
PMID: 11146820 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11146820&dopt=Abstract
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