Abstract
Alzheimer's disease (AD) is a highly incident disease in the world population, affecting about 44 million people, causing memory and cognition loss. Current treatment is based on the use of acetylcholinesterase inhibitors, which have very pronounced adverse effects such as nausea, vomiting, diarrhea and hepatotoxicity. Thus, many researchers are working to find substances, including those from natural sources, that may be of therapeutic interest in the treatment of this disease, such as curcumin (CUR), which acts directly on neuroinflammation and oxidative stress due to its antioxidant and anti-inflammatory properties, as well as inhibiting ²-amyloid plaques and tau protein hyperphosphorylation. However, some of its physicochemical properties, such as low aqueous solubility, make its use difficult. Therefore, its incorporation into mesoporous silica nanoparticles (MSNs) for nasal administration proves to be an interesting option to enable its use. MSNs may be interesting for incorporating CUR, as these systems can improve their stability and bioavailability, reducing side effects and enhancing their action. Nasal administration of this molecule can be advantageous, since the nasal mucosa presents high permeability, high blood supply and absence of first pass metabolism, avoiding the blood-brain barrier (BBB) and optimizing its action on the Nervous System via the olfactory bulb. Despite the advantages of this pathway, there are some barriers that could limit absorption, such as the mucociliary clearance mechanism, making it difficult for CUR to remain in the nasal cavity, which can be circumvented by incorporating MSNs@CUR into thermo-responsive hydrogels consisting of poloxamer and Chitosan. The objective of this work is to evaluate the potential of CUR incorporated in MSNs dispersed in thermo-responsive hydrogels in the treatment of AD. The MSNs will be obtained by direct microemulsion technique and will be characterized using physicochemical analysis and performance tests. For hydrogels, rheology, mucoadhesion, scanning and transmission electron microscopy and thermal stability tests will be performed. The study further comprises in vitro studies and the pharmacological evaluation of the animal model formulations of AD. (AU)
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