Abstract:
:The nerve growth factor (NGF) is essential for the survival of both peripheral ganglion cells and central cholinergic neurons in the basal forebrain. The accelerated loss of central cholinergic neurons during Alzheimer's disease may be a determinant cause of dementia, and this observation may suggest a possible therapeutic benefit from treatment with NGF. In recent years, convincing data have been published involving neurotrophic factors for the modulation of dopaminergic transmission within the brain and concerning the ability of NGF to prevent the degeneration of dopaminergic neurons. In this connection, the administration of NGF may slow down the progression of Parkinson's disease. However, NGF, as well as other peptidic neurotrophic factors, does not significantly penetrate the blood-brain barrier (BBB) from the circulation. Therefore, any clinical usefulness of NGF as a potential CNS therapy will depend on the use of a suitable carrier system that enhances its transport through the BBB. The present study investigates brain delivery of NGF adsorbed on poly(butyl cyanoacrylate) (PBCA) nanoparticles coated with polysorbate 80 and the pharmacological efficacy of this delivery system in the model of acute scopolamine-induced amnesia in rats as well as in the model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonian syndrome. As shown by the passive avoidance reflex (PAR) test, the intravenous administration of the nanoparticle-bound NGF successfully reversed scopolamine-induced amnesia and improved recognition and memory. This formulation also demonstrated a significant reduction of the basic symptoms of Parkinsonism (oligokinesia, rigidity, tremor). In addition, the efficient transport of NGF across the BBB was confirmed by direct measurement of NGF concentrations in the murine brain. These results demonstrate that the PBCA nanoparticles coated with polysorbate 80 are an effective carrier system for the transport of NGF to the central nervous system across the BBB following intravenous injection. This approach may improve the NGF-based therapy of age-related neurodegenerative diseases.
journal_name
J Drug Targetjournal_title
Journal of drug targetingauthors
Kurakhmaeva KB,Djindjikhashvili IA,Petrov VE,Balabanyan VU,Voronina TA,Trofimov SS,Kreuter J,Gelperina S,Begley D,Alyautdin RNdoi
10.1080/10611860903112842subject
Has Abstractpub_date
2009-09-01 00:00:00pages
564-74issue
8eissn
1061-186Xissn
1029-2330journal_volume
17pub_type
杂志文章abstract::The present investigation was aimed at targeting indinavir, a protease inhibitor to cells of mononuclear phagocyte system (MPS) via mannosylated liposomes. β-d-1-thiomannopyranoside residues were covalently coupled with dimyristoyl phosphatidylethanolamine (DMPE) to generate mannosylated-DMPE (Man-DMPE) conjugate whic...
journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
pub_type: 杂志文章,评审
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