第二代抗精神病药,喹硫平半富马酸盐(QF),对精神病的消极和积极迹象表现出高度活跃。然而,当代报道显示,QF长期治疗可导致致死性血小板减少和白细胞减少.因此,为了规避现有疗法的弊端,目前的工作旨在设计一种负载QF的生物可降解纳米乳液(QF-NE),并通过泊洛沙姆-壳聚糖进行适当的表面电荷修饰,并评估其针对RPMI-2650细胞系的靶向效率。通过O/W乳化水性滴定技术配制QF负载的泊洛沙姆-壳聚糖原位凝胶(QF-Nanoulgel),并使用QbD方法进行优化。优化的QF-Nanoululgel接受球大小的评估,PDI,zeta电位,%T,粘度,%EE,离体粘膜粘附强度为15.0±0.3nm,0.05±0.001,-18.3±0.2mV,99.8±0.8%,13.5±2.1cP,69.0±1.5%,和43.7±1.5g,分别。与QF-NE和QF悬浮液相比,QF-Nanoululgel显示出持续释放并服从零级动力学。此外,与药物和阴性对照相比,纳米制剂处理的血液样品在10小时处理后没有引起溶血活性。Further,体外细胞毒性,细胞摄取,在RPMI-2650细胞上评估12.5和25μMQF-Nanoulgel的渗透,发现其无毒,细胞渗透为0.55±0.02µg和1.1±0.04µg,分别,这确保了QF-Nanogel的安全性和效力。目前的研究表明,鼻内QF-Nanoululgel已成功开发为精神分裂症患者安全有效地递送QF的新型剂型。
Second-generation antipsychotics, quetiapine hemifumarate (QF), exhibited highly active against negative and positive signs of psychosis. However, contemporary reports have shown that long-term therapy with QF causes lethal thrombocytopenia and leukopenia. Hence, to circumvent the drawbacks of available therapies, the current work aimed to design a QF-loaded biodegradable nanoemulsion (QF-NE) with suitable surface charge modification by poloxamer-chitosan and evaluate its targeting efficiency against RPMI-2650 cell lines. QF-loaded poloxamer-chitosan in-situ gel (QF-Nanoemulgel) was formulated through the O/W emulsification aqueous titration technique and optimized using the QbD approach. Optimized QF-Nanoemulgel subjected to evaluate for globule size, PDI, zeta potential, %T, viscosity, %EE, and ex-vivo mucoadhesive strength were found to be 15.0 ± 0.3 nm, 0.05 ± 0.001, -18.3 ± 0.2 mV, 99.8 ± 0.8 %, 13.5 ± 2.1 cP, 69.0 ± 1.5 %, and 43.7 ± 1.5 g, respectively. QF-Nanoemulgel revealed sustained release and obeyed zero-order kinetics compared to QF-NE and QF-suspension. Additionally, nanoformulations treated blood samples did not cause hemolytic activity compared to drug and negative control after 10 h treatment. Further, in-vitro cytotoxicity, cellular uptake, and permeation of 12.5 and 25 μM QF-Nanoemulgel were assessed on RPMI-2650 cells and discovered nontoxic with 0.55 ± 0.02 µg and 1.1 ± 0.04 µg cellular permeation, respectively, which ensured the safety and potency of QF-Nanogel. Current research revealed the successful development of intranasal QF-Nanoemulgel as a novel dosage form for the safe and effective delivery of QF in schizophrenia patients.