Abstract
Parkinson disease is one of the common age-related motor neurodegenerative diseases, in which dopamine neurons degeneration is considered to be pathognomic for the development of motor disfunction. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which is considered to be a key regulator of neuronal plasticity. BDNF, being a large molecule, does not pass through the blood-brain barrier (BBB). Synthetic polymer nanoparticles (NP), covered by surfactant, provide the phenomenon of “Trojan hoarse” and enable BDNF to penetrate into the brain tissue. For modelling of parkinsonism we used an intraperitoneal (i.p.) injection of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which was injected to the C57BL/6 mice with subsequest treatment with normal saline (group 1), BDNF (group 2), nanoparticulate BDNF (group 3) and surfactant-coated nanoparticulate BDNF (group 4). After 90 min, 24 hours, 72 hours and 7 days manifestations of parkinsonism were evaluated using behavioural tests of open field, rota-rod, assessment of the tremor, length of the body and pace. At the end of experiment the brain was sampled for histological evaluation of changes in the striatum and midbrain and concentration of BDNF in the brain tissues. The results of the experiments demonstrated that nanoparticulate BDNF covered with surfactant significanltly reduced rigidity of the skeletal muscles, oligokinesia and tremor, and also significantly increased BDNF concentration in the brain tissues.
Highlights
The objective of this study is to evaluate neuroprotective effect of nanoparticulate Brain-derived neurotrophic factor (BDNF) sorbed on to the polylactic NP in the established model of parkinsonism caused by MPTP
Our experiments demonstrated that i.v. injection of poloxamercoated nanoparticulate BDNF loaded onto PLGA NP significantly increases concentration of neurotrophin in the brain
BDNF delivered to the brain tissues provides considerable alleviation of the symptoms of MPTP-induced parkinsonism
Summary
Analysis of modern literature revealed two main ways to solve this problem: firstly, to increase selective action of the drugs, and secondly, to provide higher concentration of the medications at the targeted structures, in the central nervous system (CNS) at the expense of directed transport of the drugs using specific carriers [1, 2]. Trying to implement the first direction, we are facing certain limitations, such as presence of the targets with equal sensitivity in different structures of the body which makes the desired selectivity not feasible; persuing the second direction, we come across another limitation, such as toxicity of the carriers for the distant delivery of the drugs, while high selectivity becomes a considerable advantage in this case. Presence of the BBB is a major limitation for the medicinal correction of the neurodegenerative diseases, tumors and other pathologies of the CNS
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