Abstract：
:Delivery of drugs into the brain is poor due to the blood brain barrier (BBB). This study describes the development of a novel liposome-based brain-targeting drug delivery system. The liposomes incorporate a diacylglycerol moiety coupled through a linker to a peptide of 5 amino acids selected from amyloid precursor protein (APP), which is recognized by specific transporter(s)/receptor(s) in the BBB. This liposomal system enables the delivery of drugs across the BBB into the brain. The brain-directed liposomal system was used in a mouse model of Parkinson's disease (PD). Intra-peritoneal (IP) administration of liposomes loaded with dopamine (DA) demonstrated a good correlation between liposomal DA dose and the behavioral effects in hemiparkinsonian amphetamine-treated mice, with an optimal DA dose of 60 µg/kg. This is significantly lower dose than commonly used doses of the DA precursor levodopa (in the mg/kg range). IP injection of the APP-targeted liposomes loaded with a DA dose of 800 µg/kg, resulted in a significant increase in striatal DA within 5 min (6.9-fold, p < 0.05), in amphetamine-treated mice. The increase in striatal DA content persisted for at least 3 h after administration, which indicates a slow DA release from the delivery system. No elevation in DA content was detected in the heart or the liver. Similar increases in striatal DA were observed also in rats and mini-pigs. The liposomal delivery system enables penetration of compounds through the BBB and may be a candidate for the treatment of PD and other brain diseases.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Kahana M,Weizman A,Gabay M,Loboda Y,Segal-Gavish H,Gavish A,Barhum Y,Offen D,Finberg J,Allon N,Gavish Mdoi
10.1038/s41380-020-0742-4subject
Has Abstractpub_date
2020-05-05 00:00:00eissn
1359-4184issn
1476-5578pii
10.1038/s41380-020-0742-4pub_type
杂志文章abstract：:Chromosome 1q has been implicated in the etiology of schizophrenia in several independent studies. However, the peak linkage findings have been dispersed over a large chromosomal region, with negative findings in this region also being reported. Our group has previously observed linkage on chromosome 1q42, maximizing ...
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pub_type： 临床试验,杂志文章
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pub_type： 临床试验,杂志文章,多中心研究
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pub_type： 杂志文章,多中心研究,随机对照试验
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