Department of Pharmaceutics, H. R. Patel Institute of Pharmaceutical Education and Research, Shirpur, 425405 Dhule (MS), India.
Department of Pharmaceutical Chemistry, H. R. Patel Institute of Pharmaceutical Education and Research, Shirpur, 425405 Dhule (MS), India.
Ann Pharm Fr. 2024 Sep;82(5):848-864. doi: 10.1016/j.pharma.2024.04.009. Epub 2024 Apr 27.
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 (R: 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.
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,本研究旨在设计载 QF 的聚乙二醇(PEG)功能化氧化石墨烯纳米片(GON),用于 QF 的鼻内给药。简而言之,使用改良的 Hummers 法合成 GO,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 功能化 GON。然后使用 π-π 堆积现象(QF@PEG-GON)将 QF 装饰在 PEG-GON 的笼上。QF@PEG-GON 纳米复合材料经历了多种光谱特性、体外药物释放、黏膜黏附研究、离体扩散研究等。QF@PEG-GON 纳米复合材料的表面形态验证了纳米复合材料的破裂性质,而纳米复合材料的衍射图谱和热图谱证实 QF 转化为无定形形式,在 PEG-GON 中均匀分布。此外,PEG-GON 的离体研究表明,由于其表面官能团和亲水性,其具有优异的黏膜黏附能力。纳米复合材料的载药量和包封效率分别为 9.2±0.62%和 92.3±1.02%。所开发的纳米复合材料在 24 小时内释放了 43.82±1.65%的药物,Korsemeyer-Peppas 模型提供了最佳拟合释放动力学(R:0.8614)。在这里,PEG-GON 的层间距阻止了缓冲液的快速扩散,导致释放模式延迟。总之,预期的 QF@PEG-GON 纳米复合材料有望成为 QF 鼻内给药的纳米载体平台。