Improved Brain Delivery of Benzylpenicillin with a Peptide-vector-mediated Strategy

Previous studies from our laboratory have demonstrated that the coupling of doxorubicin with SynB1 vector dramatically increases its brain uptake. In the present study, we have evaluated the broad application of this approach using another molecule: benzylpenicillin (B-Pc). We, therefore, have coupl...

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Bibliographic Details
Published in:Journal of drug targeting 2002-06, Vol.10 (4), p.309-315
Main Authors: Rousselle, Christophe, Clair, Philippe, Temsamani, Jamal, Scherrmann, Jean-Michel
Format: Article
Language:English
Subjects:
Amino Acid Sequence - physiology
Animals
Bbb
Benzylpenicillin
Brain - drug effects
Brain - metabolism
Brain Uptake
Capillary Depletion
Drug Delivery Systems - methods
Drug Evaluation, Preclinical
In Situ Brain Perfusion
Male
Molecular Sequence Data
Penicillin G - administration & dosage
Penicillin G - chemistry
Penicillin G - pharmacokinetics
Peptide-vector
Peptides - administration & dosage
Peptides - chemistry
Peptides - pharmacokinetics
Rats
Rats, Sprague-Dawley
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Summary:Previous studies from our laboratory have demonstrated that the coupling of doxorubicin with SynB1 vector dramatically increases its brain uptake. In the present study, we have evaluated the broad application of this approach using another molecule: benzylpenicillin (B-Pc). We, therefore, have coupled the β -lactam antibiotic B-Pc with SynB1 and assessed its ability to cross the blood-brain barrier (BBB) using the in situ rat brain perfusion method. We first confirmed the very low brain uptake of free radiolabeled B-Pc. When B-Pc was coupled to SynB1, its uptake in brain was increased by a factor of 7, without compromising the BBB integrity. The vectorised B-Pc was distributed in all the gray areas assessed (frontal, parietal, and occipital cortex, thalamus, hippocampus, and striatum). Moreover, using a wash-out procedure and a capillary depletion method, we have shown that the radiolabeled B-Pc was associated mainly with brain parenchyma. In summary, this study demonstrates the successful application of the use of SynB1 vector for the transport of B-Pc across the BBB.
ISSN:1061-186X
1029-2330
DOI:10.1080/10611860290031886