Nicotinamide loaded functionalized solid lipid nanoparticles improves cognition in Alzheimer’s disease animal model by reducing Tau hyperphosphorylation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Molood Alsadat Vakilinezhad, Azadeh Amini, Hamid Akbari Javar, Batool Faegheh Baha’addini Beigi Zarandi, Hashem Montaseri, Rassoul Dinarvand

ABSTRACT

BACKGROUND: Nicotinamide is considered to be effective in halting the Alzheimer's disease progression. The body could absorb a limited amount of nicotinamide at a time, requiring multiple doses through a day. To overcome such an obstacle which reduces the patient compliance, a sustained/controlled delivery system could be useful. METHOD: Nicotinamide loaded solid lipid nanoparticles (SLN) were prepared and functionalized with polysorbate 80 (S80), phosphatidylserine (PS) or phosphatidic acid (PA). The acquired particles were characterized and evaluated in respect of their cytotoxicity, biodistribution, and in vivo effectiveness through the different routes of administration. RESULTS: The optimum sizes of 112 ± 1.6 nm, 124 ± 0.8 nm, and 137 ± 1.05 nm were acquired for S80-, PS-, and PA-functionalized SLNs, respectively. The in vitro cytotoxicity on SH-SY5Y cell line showed the safety of formulations except for S80-functionalized SLNs. Biodistribution study of SLNs has proved the benefits of functionalization in improving the brain delivery. The results of spatial and memory test, i.e. Morris water maze, and also histopathology and biochemical tests demonstrated the effectiveness of i.p. injection of PS -functionalized SLNs in improving the cognition, preserving the neuronal cells and reducing tau hyperphosphorylation in a rat model of Alzheimer's disease. CONCLUSION: The acquired PS-functionalized SLN could be a potential brain delivery system. Loaded with nicotinamide, an HDAC inhibitor, it could ameliorate the cognition impairment of rats more effectively than the conventional administration of nicotinamide, i.e. oral, in the early stage of Alzheimer's disease. Graphical abstract ᅟ. More... »

PAGES

165-177

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s40199-018-0221-5

DOI

http://dx.doi.org/10.1007/s40199-018-0221-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1107967706

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30386982


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