Abstract：
Quetiapine Fumarate (QF) is an atypical antipsychotic with poor oral bioavailability (9%) due to its low permeability and pH-dependent solubility. Therefore, this study aims to design QF-loaded polyethylene glycol (PEG) functionalized graphene oxide nanosheets (GON) for nasal delivery of QF. In brief, GO was synthesized using a modified Hummers process, followed by ultra-sonication to produce GON. Subsequently, PEG-functionalized GON was prepared using carbodiimide chemistry (PEG-GON). QF was then decorated onto the cage of PEG-GON using the π-π stacking phenomenon (QF@PEG-GON). The QF@PEG-GON nanocomposite underwent several spectral characterizations, in vitro drug release, mucoadhesion study, ex vivo diffusion study, etc. The surface morphology of QF@PEG-GON nanocomposite validates the cracked nature of the nanocomposite, whereas the diffractograms and thermogram of nanocomposite confirm the conversion of QF into an amorphous form with uniform distribution in PEG-GON. Moreover, an ex vivo study of PEG-GON demonstrates superior mucoadhesion capacity due to its surface functional groups and hydrophilicity. The percent drug loading content and percent entrapment efficiency of the nanocomposite were found to be 9.2±0.62% and 92.3±1.02%, respectively. The developed nanocomposite exhibited 43.82±1.65% drug release within 24h, with the Korsemeyer-Peppas model providing the best-fit release kinetics (R2: 0.8614). Here, the interlayer spacing of PEG-GON prevented prompt diffusion of the buffer, leading to a delayed release pattern. In conclusion, the anticipated QF@PEG-GON nanocomposite shows promise as a nanocarrier platform for nasal delivery of QF.
摘要：
富马酸喹硫平（QF）是一种非典型抗精神病药，由于其低渗透性和pH依赖性溶解度，口服生物利用度差（9％）。因此,这项研究旨在设计QF负载的聚乙二醇（PEG）功能化的氧化石墨烯纳米片（GON）用于QF的鼻递送。简而言之,GO是使用改良的Hummers工艺合成的，然后进行超声处理以产生GON。随后，使用碳二亚胺化学(PEG-GON)制备PEG-官能化的GON。然后使用π-π堆叠现象(QF@PEG-GON)将QF装饰到PEG-GON的笼上。QF@PEG-GON纳米复合材料经历了几个光谱表征，体外药物释放，粘膜粘附研究，离体扩散研究，等。QF@PEG-GON纳米复合材料的表面形貌验证了纳米复合材料的开裂性质，而纳米复合材料的衍射图和热谱图证实了QF转化为在PEG-GON中均匀分布的无定形形式。此外，PEG-GON的离体研究表明,由于其表面官能团和亲水性,具有优异的粘膜粘附能力。纳米复合材料的载药量百分比和包封效率百分比分别为9.2±0.62%和92.3±1.02%，分别。开发的纳米复合材料在24小时内表现出43.82±1.65％的药物释放，Korsemeyer-Peppas模型提供了最适合的释放动力学（R2：0.8614）。这里,PEG-GON的层间间距防止了缓冲液的迅速扩散，导致延迟释放模式。总之,预期的QF@PEG-GON纳米复合材料有望作为经鼻递送QF的纳米载体平台。
