RESEARCH ARTICLE – Pharmaceutical NanotechnologyIntranasal Piperine-Loaded Chitosan Nanoparticles as Brain-Targeted Therapy in Alzheimer's Disease: Optimization, Biological Efficacy, and Potential Toxicity
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INTRODUCTION
Alzheimer’s disease (AD) is the most common cause of dementia worldwide; it affects more than 35 million people, and this number is expected to triple in the next 40 years because of the increase in life expectancy.1 AD is a neurodegenerative disorder that is characterized by not only progressive impairment of memory and cognitive functions but also disturbances in behavior.2., 3.
A smaller proportion (5%–10%) of all Alzheimer cases was reported to be caused by genetic abnormalities of
Materials
Chitosan with medium molecular weight (Mw = 100,000–300,000 Da) and degree of deacetylation > 90% and PIP (Mw = 285.34 Da, purity 98%) were purchased from Alpha Aeser (Ward Hill, MA 01835, United States, Massachusetts), sodium TPP was purchased from Sigma–Aldrich (St. Louis, Missouri). Poloxamer 188, Tween 80, glacial acetic acid, methanol AR, and all other reagents were of analytical grade. Colchicine, donepezil hydrochloride, thiobarbituric acid (TBA), trichloracetic acid (TCA), nitroblue
Preparation and Characterization of CS-NPs
Elaboration of various nanocarriers for solving drug delivery obstacles have been recently adopted by our work group31., 36., 37., 53., 54., 55., 56., 57., 58., 59. Among others, cross-linked CS-NPs have been rationally selected in this article and prepared by ionic gelation method.33 The latter offers simple and mild preparation conditions in aqueous environment and relies on the pH-dependent electrostatic interaction between positively charged amino groups in CS and the negatively charged
CONCLUSIONS
In the current study, hydrophobic drug PIP could be successively loaded in hydrophilic CS NPs with high entrapment and ZP sufficient for stabilization. Impact of nine optimization factors (CS solution concentration, CS:TPP ratio, stirring rate, stabilizer incorporation, CS temperature, homogenization, loading dose, and loading method) on size tuning of NPs was investigated. Adjusted interplay between such factors could elaborate the desired PS fitting the cut off for brain delivery. PIP
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