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载丙泊酚的脂质体凝胶经皮给药的优化。

Optimization of propofol loaded niosomal gel for transdermal delivery.

机构信息

Department of Anesthesiology, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, China.

IVF laboratory, Center for Reproductive Medicine, Shandong University, Jinan, Shandong, China.

出版信息

J Biomater Sci Polym Ed. 2021 May;32(7):858-873. doi: 10.1080/09205063.2021.1877064. Epub 2021 Feb 4.

Abstract

Propofol is an oily liquid widely used for rapid onset of anaesthesia intravenous route, which shows major limitations of hypersensitivity, anaphylactic reactions and pain. The aim of the present work was to bypass the above issues by formulating tailored niosomal gel to deliver propofol non-invasive transdermal route. The niosomes were prepared by film hydration method and sonication using cholesterol and Span 80. The Box Behnken design (BBD) was applied to optimize the size (93.5 nm) and the entrapment efficacy (81.5%) of the niosomes by selecting cholesterol at 139 mg, Span 80 at 0.525% and sonication time at 5.13 min. The scanning electron microscopy image showed spherical shape niosomes with smooth surface without aggregation. The release data showed significant improvement in the propofol release (92.2% after 10 h) using niosomes in comparison to the control propofol gel (with 30% methanol) without niosomes (25.3% after 10 h). The pharmacokinetic parameters in the rat model confirmed the improvement in the relative bioavailability with optimized niosomal gel (relative bioavailability = 12.12) in comparison to the control propofol gel. In conclusion, the niosomal gel offered a potential alternative non-invasive route to deliver propofol for procedural sedation especially in pediatric population.

摘要

丙泊酚是一种油性液体,广泛用于静脉途径的快速麻醉诱导,但其具有过敏反应、过敏性反应和疼痛等主要局限性。本工作旨在通过配制定制的非离子囊泡凝胶来绕过上述问题,以非侵入性透皮途径输送丙泊酚。非离子囊泡通过薄膜水化法和胆固醇与 Span 80 的超声处理制备。采用 Box-Behnken 设计(BBD)通过选择胆固醇 139mg、Span 80 0.525%和超声时间 5.13min,优化非离子囊泡的粒径(93.5nm)和包封效率(81.5%)。扫描电子显微镜图像显示非离子囊泡为球形,表面光滑,无聚集。释放数据显示,与不含非离子囊泡的对照丙泊酚凝胶(含 30%甲醇)相比,使用非离子囊泡显著改善了丙泊酚的释放(10h 后释放 92.2%)。在大鼠模型中的药代动力学参数证实,与对照丙泊酚凝胶相比,优化的非离子囊泡凝胶(相对生物利用度=12.12)提高了相对生物利用度。总之,非离子囊泡凝胶为丙泊酚的程序性镇静提供了一种潜在的非侵入性替代给药途径,特别是在儿科人群中。

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