Background

Isoformononetin (IFN) is a methoxyl derivative of daidzein and has been stated as a potent osteogenic isoflavone. However, IFN has low oral bioavailability. Advancement in the technology has led to the development of newer drug carrier systems, featuring the delivery of drugs with low oral bioavailability to advance their clinical application.

Methods

The IFN nanoemulsion (IFN-NE) was developed and optimized using the design of the experiment tool and technique approaches.

Results

The optimized IFN-NE has a particle size of 174.65 ± 1.63 nm, PDI of 0.244 ± 0.004, and zeta potential of − 30.69 ± 4.99 mV, respectively. The TEM images of optimized IFN-NE showed the spherical globular size of the nanoemulsion. The entrapment efficiency showed higher entrapment of IFN in the NE (96.04 ± 1.28%). The compatibility of IFN with excipients was confirmed by physical state characterization such as FTIR and DSC, illustrating no interaction. Optimized IFN-NE formulation was stable at different temperature conditions. In comparison to a free drug suspension, IFN-NE showed sustained drug release over a 24-h period of time. Additionally, in situ, single-pass intestinal perfusion (SPIP) results displayed significant enhancement of IFN permeability through the intestine of rats from IFN-NE when compared to free IFN.

Conclusions

Pharmacokinetics results revealed the enhanced relative oral bioavailability of IFN-NE compared to IFN suspension using female Sprague–Dawley (SD) rats as animal models. The developed IFN-NE can be a promising candidate to overcome the low oral bioavailability of IFN.

Graphical Abstract

中文翻译：

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通过纳米乳剂增强异芒柄花素的口服生物利用度：开发、优化和表征

背景

异佛芒菌素 (IFN) 是大豆苷元的甲氧基衍生物，被认为是一种有效的成骨异黄酮。然而，干扰素的口服生物利用度较低。技术的进步促进了新型药物载体系统的开发，其特点是输送口服生物利用度较低的药物，以促进其临床应用。

方法

利用实验工具和技术方法的设计开发和优化了干扰素纳米乳（IFN-NE）。

结果

优化后的 IFN-NE 粒径为 174.65 ± 1.63 nm，PDI 为 0.244 ± 0.004，zeta 电位为 − 30.69 ± 4.99 mV。优化的 IFN-NE 的 TEM 图像显示纳米乳液的球形尺寸。包封率显示 NE 中 IFN 的包封率较高 (96.04 ± 1.28%)。IFN 与赋形剂的相容性通过 FTIR 和 DSC 等物理状态表征得到证实，表明没有相互作用。优化后的IFN-NE制剂在不同温度条件下均稳定。与游离药物混悬液相比，IFN-NE 显示出 24 小时内的持续药物释放。此外，原位单次肠道灌注（SPIP）结果显示，与游离干扰素相比，干扰素-NE 显着增强了大鼠肠道的干扰素渗透性。

结论

使用雌性 Sprague-Dawley (SD) 大鼠作为动物模型，药代动力学结果显示，与 IFN 混悬液相比，IFN-NE 的相对口服生物利用度增强。开发的 IFN-NE 可能是克服 IFN 口服生物利用度低的问题的有前途的候选药物。

图形概要