Customized Intranasal Hydrogel Delivering Methylene Blue Ameliorates Cognitive Dysfunction against Alzheimer's...

Area of Science:

• Neuroscience
• Biomaterials Science
• Pharmacology

Background:

• Alzheimer's disease (AD) is characterized by tau protein aggregation, mitochondrial dysfunction, and oxidative stress.
• The blood-brain barrier (BBB) presents a significant challenge for effective AD drug delivery.
• Nasal drug delivery offers a promising route to bypass the BBB and target the brain.

Purpose of the Study:

• To develop a novel black phosphorus-methylene blue (BP-MB) nanocomposite for targeted brain delivery.
• To formulate a thermosensitive hydrogel for intranasal (IN) administration of BP-MB.
• To evaluate the therapeutic efficacy of IN BP-MB@Gel in Alzheimer's disease mouse models.

Main Methods:

• Fabrication of BP-MB nanocomposite and a thermosensitive hydrogel via cross-linking carboxymethyl chitosan and aldehyde Pluronic F127 (F127-CHO).
• Incorporation of BP-MB into the hydrogel to form BP-MB@Gel for IN delivery.
• Assessment of therapeutic effects including tau neuropathology suppression, mitochondrial function restoration, neuroinflammation alleviation, and cognitive improvement in AD mouse models.

Main Results:

• The developed BP-MB@Gel hydrogel exhibited high nasal mucosal retention and controlled drug release.
• Intranasal administration of BP-MB@Gel successfully delivered the drug to the brain.
• The treatment demonstrated synergistic effects, including reduced tau pathology, improved mitochondrial function, and decreased neuroinflammation, leading to cognitive recovery in AD mice.

Conclusions:

• Intranasal delivery of BP-MB@Gel represents a viable strategy for brain-targeted drug delivery in AD.
• The combination of black phosphorus as a carrier/antioxidant and methylene blue as a tau inhibitor shows therapeutic potential.
• This approach offers a promising avenue for managing the complex pathologies associated with Alzheimer's disease.