Synthesis and characterization of fullerene-based nanocarrier for targeted delivery of quercetin to the brain

<b>Aim:</b> Preparation of quercetin fullerene conjugate (QFC) for nose-to-brain delivery and their <i>in vitro</i> and <i>ex vivo</i> characterizations. <b>Methods:</b> Carboxylated fullerene was converted into acetylated fullerene and quercetin was conjugated and physically adsorbed on acetylated fullerene. <b>Results:</b> The particle size and zeta potential of QFC and chitosan-coated QFC (CC-QFC) were found to be 179.2 ± 1.10, 293.4 ± 2.757, -5.28 ± 1.43 and 11.6 ± 0.4 respectively. The entrapment efficiency, loading efficiency of QFC were found to be 85.55% and 42.77%. The MTT assay revealed 80.69% SH-SY5Y cell viability at a concentration of 50 μg/ml. CC-QFC showed remarkable (89.20%) <i>ex vivo</i> mucoadhesive properties compared with QFC (66.67%). Further study showed no significant ciliotoxicity by CC-QFC. <b>Conclusion:</b> The obtained results suggested the potential of CC-QFC for treatment in Alzheimer's disease. In our study, we developed a new method to deliver a natural substance called quercetin into the brain for the treatment of Alzheimer's disease. Quercetin is known for its health benefits, especially in protecting brain cells. We combined quercetin with a tiny carbon-based material called fullerene, which looks like a soccer ball, to create a new compound called quercetin fullerene conjugate (QFC). This QFC was designed to help quercetin reach the brain more effectively. To make it even better at reaching the brain, we coated QFC with a substance called chitosan. Coating it with chitosan can help to adhere it to nasal cavity for longer time for the delivery of quercetin to the brain. Importantly, our studies showed that this modified form of quercetin did not harm brain cells or the lining of the nose. Overall, our findings suggest that this new approach could be a promising way to develop treatments for Alzheimer's disease. Nanosized quercetin fullerene conjugate was prepared for the management of Alzheimer's disease and further coated with chitosan to enhance the nasal residence. Chitosan-coated quercetin fullerene conjugate (CC-QFC) for the effective delivery of quercetin into the brain via nasal route. First, we synthesized carboxylated fullerene. Then, acetylated fullerene was synthesized using chemical transformation into acylated fullerene. CC-QFC was obtained by simple coating with chitosan solution. Confirmed using FT-IR and ¹H-NMR Spectrometry. SEM and HR-TEM reveal the unique spherical morphology of QFC. The CC-QFC showed adequate mucoadhesive properties, as the nanoparticle contains chitosan polymer in the formulation which provides mucoadhesion and increases the residential time of nanoparticles with nasal mucosa. QFC was found to be 85.55% and 42.77%, entrapment efficiency and loading efficiency respectively with sustained release observed over 72 h, indicating potential for prolonged therapeutic effect. <i>In vitro</i> studies demonstrate promising results with low cytotoxicity on neuronal cells and minimal nasal ciliotoxicity, suggesting safety and efficiency for treatment.