盐酸鲁拉西酮负载niosomes增强鼻给药抗精神病潜能的工程设计

S. Bhatt, Sumit Sharma, J. Sharma, Manish Kumar, R. Verma, Deepak Kaushik
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引用次数: 0

摘要

具有高首过代谢或易受酶降解的药物可通过鼻腔给药以避免其降解。鲁拉西酮与利培酮、齐拉西酮、氯氮平等姊妹药相比,具有较低的毒副作用。采用醚注射法制备鲁拉西酮乳质体,并采用中心复合设计对其进行优化。采用优化后的配方进行体外和体内研究。结果表明,优化后的配方粒径为159.02±0.58 nm,包封效率为91.6±1.6%。鼻腔组织病理学分析结果表明,优化后的配方对鼻黏膜无刺激性和无毒性。体外实验结果显示,最佳处方F7在24 h内的释药率为94.61±0.27%。体内(白化Wistar大鼠)研究结果表明,与市面上销售的片剂(Lurasid®40 mg)和纯药物混悬液相比,各种药代动力学参数(Cmax、Tmax、AUC(0-24)、T1/2、Vd和Cl)和药效学参数(条件回避反应、利用超氧化物歧化酶、丙二醛和谷胱甘肽等氧化标志物进行生化评价)均有显著改善。经鼻给药后,优化配方F-7的生物利用度是纯混悬液的4.9倍。这些发现表明,盐酸鲁拉西酮鼻腔乳质体制剂是一个很有前途的纳米平台,可以提高鲁拉西酮的整体性能。这些结果可能为纳米医学的未来开辟新的道路。
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Engineering of Lurasidone hydrochloride loaded niosomes for enhancing the antipsychotic potential for nasal administration
Drugs with high first-pass metabolism or that are susceptible to enzymatic degradation can be administered through the nasal route to avoid their degradation. Lurasidone exhibits less toxicity and side effects as compared to its sister drugs like risperidone, ziprasidone, clozapine, etc. The present study aimed to develop Lurasidone loaded niosomes for nasal delivery. Lurasidone niosomes were developed by adapting the ether injection method and optimized using a central composite design. In vitro and in vivo studies were conducted using optimized formulation. The findings showed that the optimized formulation exhibited a particle size of 159.02 ± 0.58 nm and an entrapment efficiency of 91.6 ± 1.6 %. The findings from the nasal histopathological analysis revealed that the optimized formulation was non-irritant and non-toxic for nasal mucosa. The findings from in vitro studies revealed 94.61 ± 0.27 % of drug release from optimized formulation F7 throughout 24 hrs. The findings of in vivo (Albino Wistar rats) studies demonstrated that various pharmacokinetic parameters (Cmax, Tmax, AUC(0-24), T1/2, Vd and Cl) and pharmcodynamic parameters (conditioned avoidance response, biochemical estimation using oxidative markers such as superoxide dismutase, malondialdehyde and glutathione) were significantly improved compared to marketed tablets (Lurasid® 40 mg) and pure drug suspension. Optimized formulation F-7 exhibited 4.9 times more bioavailability than that of pure drug suspension following intranasal administration. These findings indicate that nasal niosomal formulation of Lurasidone HCl is a promising nanoplatform for enhancing the overall performance of Lurasidone. These results could open new avenues into the future of nanomedicine.
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来源期刊
Current Nanomedicine
Current Nanomedicine Medicine-Medicine (miscellaneous)
CiteScore
2.00
自引率
0.00%
发文量
15
期刊最新文献
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