Lycopene is considered as a promising neuroprotector with multiple bioactivities, while its therapeutic use in neurological disorders is restricted due to low solubility, instability and limited bioavailability. Our work aimed to develop lycopene-loaded microemulsion (LME) and investigate its potentials in improving bioavailability and brain-targeting efficiency following oral administration. The blank microemulsion (ME) excipients were selected based on orthogonal design and pseudo-ternary phase diagrams, and LME was prepared using the water titration method and characterized in terms of stability, droplet size distribution, zeta potential, shape and lycopene content. The optimized LME encompassed lycopene, (R)-(+)-limonene, Tween 80, Transcutol HP and water and lycopene content was 463.03 ± 8.96 µg/mL. This novel formulation displayed transparent appearance and satisfactory physical and chemical stabilities. It was spherical and uniform in morphology with an average droplet size of 12.61 ± 0.46 nm and a polydispersity index (PDI) of 0.086 ± 0.028. The pharmacokinetics and tissue distributions of optimized LME were evaluated in rats and mice, respectively. The pharmacokinetic study revealed a dramatic 2.10-fold enhancement of relative bioavailability with LME against the control lycopene dissolved in olive oil (LOO) dosage form in rats. Moreover, LME showed a preferential targeting distribution of lycopene toward brain in mice, with the value of drug targeting index (DTI) up to 3.45. In conclusion, the optimized LME system demonstrated excellent physicochemical properties, enhanced oral bioavailability and superior brain-targeting capability. These findings provide a basis for the applications of ME-based strategy in brain-targeted delivery via oral route, especially for poorly water-soluble drugs.

中文翻译：

---

番茄红素微乳口服给药用于脑靶向：制备，表征，药代动力学评估和组织分布。

番茄红素被认为是具有多种生物活性的有前途的神经保护剂，而其在神经系统疾病中的治疗用途由于溶解度低，不稳定和生物利用度有限而受到限制。我们的工作旨在开发番茄红素负载型微乳剂（LME），并研究其在口服后改善生物利用度和脑靶向效率方面的潜力。根据正交设计和拟三元相图选择空白微乳液（ME）赋形剂，并使用水滴定法制备LME，并根据稳定性，液滴尺寸分布，ζ电位，形状和番茄红素含量对其进行表征。优化的LME包括番茄红素，（R）-（+）-柠檬烯，吐温80，Transcutol HP和水，番茄红素含量为463.03±8.96 µg / mL。这种新颖的配方显示出透明的外观以及令人满意的物理和化学稳定性。它是球形的，形态均匀，平均液滴尺寸为12.61±0.46 nm，多分散指数（PDI）为0.086±0.028。分别在大鼠和小鼠中评估了优化的LME的药代动力学和组织分布。药代动力学研究表明，LME相对于大鼠中溶于橄榄油（LOO）剂型的对照番茄红素的相对生物利用度显着提高了2.10倍。此外，LME在小鼠中显示出番茄红素向大脑的优先靶向分布，药物靶向指数（DTI）值高达3.45。总之，优化的LME系统具有出色的理化特性，增强的口服生物利用度和出色的脑靶向能力。