Purpose

This study aimed to develop and optimize lutein-loaded solid lipid nanoparticles (Lu-SLN) for ocular delivery. The objective was to achieve the mean particle size of Lu-SLN less than 100 nm, sustain the drug release up to 8 h, and evaluate the corneal permeation parameters of the optimized batch.

Methods

Lu-SLN were prepared by hot homogenization and cold dilution method. The Plackett-Burman screening design and 3² full factorial design were adopted sequentially to study the effect of various formulation and process variables, and further optimized with the help of desirability function.

Results

The statistical designs revealed that the amount of Gelucire® 44/14 and homogenization speed had a significant effect (P < 0.05) on the mean particle size and % drug release of Lu-SLN. The optimized formulation prepared with the help of the desirability function showed a mean particle size of 79.70 nm and sustained the drug release up to 8 h in simulated tear fluid. The apparent permeability coefficient and steady-state flux of the optimized batch were found to be \(1.09 \times {10}^{-4}\frac{\mathrm{cm}}{\mathrm{h}}\) and \(7.33 \times {10}^{-2}\frac{{\mu \mathrm{g}}}{{\mathrm{cm}}^{2}}/\mathrm{h}\), respectively, and the corneal hydration was found to be 78.35%.

Conclusions

Lu-SLN with chosen objectives can be successfully prepared by hot homogenization technique and ex vivo evaluation revealed that optimized formulation avoided any damage to the cornea.

Graphical abstract

中文翻译：

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叶黄素负载脂质脂质体纳米颗粒的眼部递送：统计优化和体内评价。

目的

这项研究旨在开发和优化负载叶黄素的固体脂质纳米颗粒（Lu-SLN）进行眼部递送。目的是使Lu-SLN的平均粒径小于100 nm，维持药物释放长达8 h，并评估优化批次的角膜渗透参数。

方法

通过热均质和冷稀释法制备Lu-SLN。依次采用Plackett-Burman筛选设计和3 ²全因子设计来研究各种配方和工艺变量的影响，并在期望功能的帮助下进一步进行优化。

结果

统计设计表明，Gelucire®44/14的量和均质化速度 对Lu-SLN的平均粒径和药物释放％有显着影响（P <0.05）。借助所需功能制备的优化配方显示出平均粒径为79.70 nm，并在模拟泪液中维持长达8小时的药物释放。发现优化批次的表观渗透系数和稳态通量为\（1.09 \ times {10} ^ {-4} \ frac {\ mathrm {cm}} {\ mathrm {h}} \）和\分别（7.33 \ times {10} ^ {-2} \ frac {{\ mu \ mathrm {g}}} {{\ mathrm {cm}} ^ {2}} / \ mathrm {h} \）和发现角膜水合率为78.35％。

结论

具有选定目标的Lu-SLN可以通过热均质技术成功制备，离体评估显示优化配方避免了对角膜的任何损害。

图形概要