Journal
DRUG DESIGN DEVELOPMENT AND THERAPY
Volume 10, Issue -, Pages 417-429Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S97982
Keywords
chitosan; spray drying; microsphere; Alzheimer's disease; phospholipids
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Funding
- National Key Technology Research and Development Program of the Ministry of Science and Technology, China [2013GA740103]
- National Natural Science Foundation of China [81573717]
- Natural Science Foundation of Shandong Province [ZR2012CM025, ZR2013HL066]
- Department of Science and Technology of Weifang [2014WS045]
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Cholinergic neurotransmission loss is the main cause of cognitive impairment in patients with Alzheimer's disease. Phospholipids (PLs) play an essential role in memory and learning abilities. Moreover, PLs act as a source of choline in acetylcholine synthesis. This study aimed to prepare and optimize the formulation of chitosan/phospholipid/beta-cyclodextrin (CTS/PL/beta-CD) microspheres that can improve cognitive impairment. The CTS/PL/beta-CD microspheres were prepared by spray drying, and optimized with an orthogonal design. These microspheres were also characterized in terms of morphology, structure, thermostability, drug loading, and encapsulation efficiency. The spatial learning and memory of rats were evaluated using the Morris water maze test, and the neuroprotective effects of the CTS/PL/beta-CD microspheres were investigated by immunohistochemistry. Scanning electron microscopic images showed that the CTS/PL/beta-CD microspheres were spherical with slightly wrinkled surfaces. Fourier transform infrared spectroscopy and differential scanning calorimetry proved that PLs formed hydrogen bonds with the amide group of CTS and the hydroxyl group of beta-CD. The learning and memory abilities of rats in the treated group significantly improved compared with those in the model group. Immunohistochemical analysis revealed that treatment with the CTS/PL/beta-CD microspheres attenuated the expression of protein kinase C-delta and inhibited the activation of microglias. These results suggest that the optimized microspheres have the potential to be used in the treatment of Alzheimer's disease.
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