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纳米囊泡分散体制备及其用于更昔洛韦口服给药的研究与评价。

Development and evaluation of nanosized niosomal dispersion for oral delivery of Ganciclovir.

机构信息

Nanoformulation Research Lab, Faculty of Pharmacy, Hamdard University, New Delhi, India.

出版信息

Drug Dev Ind Pharm. 2012 Jan;38(1):84-92. doi: 10.3109/03639045.2011.592529. Epub 2011 Jul 4.

Abstract

Encapsulation of Ganciclovir in lipophilic vesicular structure may be expected to enhance the oral absorption and prolong the existence of the drug in the systemic circulation. So the purpose of the present study was to improve the oral bioavailability of Ganciclovir by preparing nanosized niosomal dispersion. Niosomes were prepared from Span40, Span60, and Cholesterol in the molar ratio of 1:1, 2:1, 3:1, and 3:2 using reverse evaporation method. The developed niosomal dispersions were characterized for entrapment efficiency, size, shape, in vitro drug release, release kinetic study, and in vivo performance. Optimized formulation (NG8; Span60:Cholesterol 3:2 molar ratio) has shown a significantly high encapsulation of Ganciclovir (89±2.13%) with vesicle size of 144±3.47 nm (polydispersity index [PDI]=0.08). The in vitro release study signifies sustained release profile of niosomal dispersions. Release profile of prepared formulations have shown that more than 85.2±0.015% drug was released in 24 h with zero-order release kinetics. The results obtained also revealed that the types of surfactant and Cholesterol content ratio altered the entrapment efficiency, size, and drug release rate from niosomes. In vivo study on rats reveals five-time increment in bioavailability of Ganciclovir after oral administration of optimized formulation (NG8) as compared with tablet. The effective drug concentration (>0.69 µg/mL in plasma) was also maintained for at least 8 h on administration of the niosomal formulation. In conclusion, niosomes can be proposed as a potential oral delivery system for the effective delivery of Ganciclovir.

摘要

将更昔洛韦包封在亲脂性囊泡结构中有望提高其口服吸收并延长药物在全身循环中的存在时间。因此,本研究旨在通过制备纳米尺寸的非离子型脂质体分散体来提高更昔洛韦的口服生物利用度。非离子型脂质体是由 Span40、Span60 和胆固醇以摩尔比 1:1、2:1、3:1 和 3:2 用逆向蒸发法制备的。对所开发的非离子型脂质体分散体进行包封效率、粒径、形态、体外药物释放、释放动力学研究和体内性能进行了表征。优化的配方(NG8;Span60:胆固醇摩尔比 3:2)显示出更昔洛韦的高包封率(89±2.13%),囊泡粒径为 144±3.47nm(多分散指数[PDI]=0.08)。体外释放研究表明非离子型脂质体分散体具有持续释放的特征。制备的制剂的释放曲线表明,24 小时内超过 85.2±0.015%的药物以零级释放动力学释放。所得结果还表明,表面活性剂的类型和胆固醇含量比改变了非离子型脂质体的包封效率、粒径和药物释放速率。在大鼠体内研究中,与片剂相比,口服优化配方(NG8)后,更昔洛韦的生物利用度增加了五倍。在给予非离子型脂质体制剂后,至少 8 小时内血浆中有效药物浓度(>0.69μg/ml)也得以维持。总之,非离子型脂质体可以作为一种有前途的口服给药系统,用于有效递更昔洛韦。

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