Improved brain uptake and pharmacological activity of dalargin using a peptide-vector-mediated strategy Journal Article
| Authors: | Rousselle, C.; Clair, P.; Smirnova, M.; Kolesnikov, Y.; Pasternak, G. W.; Gac-Breton, S.; Rees, A. R.; Scherrmann, J. M.; Temsamani, J. |
| Article Title: | Improved brain uptake and pharmacological activity of dalargin using a peptide-vector-mediated strategy |
| Abstract: | The blood-brain barrier restricts the passage of substances into the brain. Neuropeptides, such as enkephalins, cannot be delivered into the brain when given systemically because of this barrier. Therefore, there is a need to develop efficient transport systems to deliver these drugs to the brain. Recently, we have demonstrated that conjugation of doxorubicin or penicillin to peptide vectors significantly enhances their brain uptake. In this study, we have conjugated the enkephalin analog dalargin with two different peptide vectors, SynB1 and SynB3, to improve its brain delivery and its pharmacological effect. We show by in situ brain perfusion that vectorization markedly enhances the brain uptake of dalargin. We also show using the hot-plate model that this enhancement in brain uptake results in a significant improvement in the observed antinociceptive effect of dalargin. These results support the usefulness of peptide-mediated strategies for improving the availability and efficacy of central nervous system drugs. |
| Keywords: | controlled study; unclassified drug; doxorubicin; drug efficacy; nonhuman; mouse; animals; mice; animal tissue; animal experiment; drug structure; peptide; structure activity relation; drug receptor binding; drug delivery systems; drug distribution; drug uptake; brain; blood brain barrier; blood-brain barrier; peptides; penicillin derivative; analgesia; drug transport; neuropeptide; biological transport; drug conjugation; drug delivery system; drug formulation; analgesic activity; hot plate test; brain perfusion; antinociception; enkephalin; central nervous system agents; priority journal; article; leucine enkephalin[2 dextro alanine 6 arginine]; protein synb1; protein synb3; peptide vector; enkephalin, leucine-2-alanine |
| Journal Title: | Journal of Pharmacology and Experimental Therapeutics |
| Volume: | 306 |
| Issue: | 1 |
| ISSN: | 0022-3565 |
| Publisher: | American Society for Pharmacology and Experimental Therapeutics |
| Date Published: | 2003-07-01 |
| Start Page: | 371 |
| End Page: | 376 |
| Language: | English |
| DOI: | 10.1124/jpet.102.048520 |
| PUBMED: | 12682214 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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414Pasternak
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