Neuroinflammation is a central mechanism in the development and progression of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. The blood-brain barrier (BBB) poses a major obstacle to effective drug delivery, limiting therapeutic access to the brain. Traditional systemic administration often fails to achieve sufficient drug concentrations at the target site, leading to reduced efficacy and increased side effects. To address this challenge, researchers have turned to intranasal delivery—a non-invasive route that allows direct transport of therapeutics from the nasal cavity to the brain along olfactory and trigeminal nerve pathways, bypassing the BBB.
In this study, a novel dual-targeting nanocarrier system was developed using fucoidan and chitosan to enhance the delivery of curcumin, a natural polyphenol with potent anti-inflammatory and neuroprotective properties. Curcumin’s clinical utility is restricted by its poor aqueous solubility, rapid metabolism, and low bioavailability. Encapsulation within biocompatible nanocarriers offers a promising solution by improving solubility, protecting the drug from degradation, and enabling targeted delivery.
Fucoidan, a sulfated polysaccharide derived from marine algae, has been shown to bind specifically to P-selectin, a cell adhesion molecule overexpressed on activated endothelial cells and platelets during inflammation.IL-2 Antibody In Vitro Chitosan, a cationic polysaccharide, exhibits pH-responsive behavior due to protonation of its amino groups under acidic conditions—common in inflamed tissues.BHMT Antibody MedChemExpress By combining these two polymers, the resulting nanocarriers were designed to respond simultaneously to both pathological pH and P-selectin expression, enabling precise targeting to inflamed brain regions.
The Cur-F/CS nanocarriers were fabricated through ionotropic crosslinking, forming stable nanoparticles with an average size of approximately 170 nm and zeta potential of +25 mV. Characterization using FTIR and XRD confirmed successful encapsulation of curcumin, with no significant crystalline peaks observed, indicating molecular dispersion within the polymer matrix. In vitro release studies demonstrated sustained curcumin release at pH 6.0, mimicking the inflammatory microenvironment, suggesting enhanced retention and controlled delivery.
Cellular uptake experiments using LPS-stimulated BV2 microglial cells revealed significantly higher curcumin accumulation in cells treated with Cur-F/CS NCs compared to free curcumin, especially under acidic conditions (pH 5–6). Fluorescence imaging confirmed preferential internalization via endocytic pathways, driven by electrostatic interactions between cationic chitosan and negatively charged cell membranes, as well as P-selectin-mediated binding.
In vivo evaluation in an LPS-induced mouse model of neuroinflammation showed that intranasally administered Cur-F/CS NCs achieved superior brain biodistribution. Fluorescent imaging revealed strong signal intensity in the cerebral cortex, hippocampus, and hypothalamus—regions heavily affected by inflammation—compared to minimal signal in control groups. Quantitative analysis indicated a 20-fold increase in brain accumulation relative to free curcumin.
Histopathological analysis of brain tissue sections demonstrated reduced neuronal damage, decreased glial activation, and lower levels of pro-inflammatory markers such as IL-6 and TNF-α.PMID:35083238 These findings correlate with improved functional outcomes, including reduced cognitive deficits and motor impairments in treated animals.
This dual-targeting strategy leverages the biological signatures of inflamed tissues—acidic pH and P-selectin expression—to guide nanocarriers precisely to lesion sites. By enhancing drug retention and minimizing off-target exposure, the system improves therapeutic efficiency while reducing dosage frequency and potential toxicity.
These results highlight the transformative potential of smart nanocarriers in treating CNS disorders. The integration of stimuli-responsive materials with biological targeting ligands opens new avenues for precision medicine in neurology. Future work will focus on scaling up production, assessing long-term safety, and advancing toward clinical trials. With further refinement, this intranasal delivery platform could become a cornerstone in the management of chronic brain inflammation, offering a safe, effective, and patient-friendly alternative to invasive treatments.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com
