Lipid-based drug formulations are promising systems for improving delivery of drugs to ocular tissues, such as retina. To develop lipid-based systems further, an improved understanding of their pharmacokinetics is required, but high-quality in vivo experiments require a large number of animals, raising ethical and economic questions. In order to expedite in vivo kinetic testing of lipid-based systems, we propose a barcode approach that is based on barcoding liposomes with non-endogenous lipids. We developed and evaluated a liquid-chromatography-mass spectrometry method to quantify many liposomes simultaneously in aqueous humor, vitreous, and neural retina at higher than ±20% precision and accuracy. Furthermore, we showed in vivo suitability of the method in pharmacokinetic evaluation of six different liposomes after their simultaneous injection into the rat vitreal cavity. We calculated pharmacokinetic parameters in vitreous and aqueous humor, quantified liposome concentrations in the retina, and quantitated retinal distribution of the liposomes in the rats. Compared to individual injections of the liposome formulations, the barcode-based study design enabled reduction of animal numbers from 72 to 12. We believe that the proposed approach is reliable and will reduce and refine ocular pharmacokinetic experiments with liposomes and other lipid-based systems.

中文翻译：

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用于眼组织中脂质体绝对定量的条形码脂质


基于脂质的药物制剂是改善药物向眼组织（例如视网膜）输送的有前景的系统。为了进一步开发基于脂质的系统，需要更好地了解其药代动力学，但高质量的体内实验需要大量动物，这就引发了伦理和经济问题。为了加快基于脂质的系统的体内动力学测试，我们提出了一种基于具有非内源性脂质的条形码脂质体的条形码方法。我们开发并评估了一种液相色谱-质谱法，可以同时定量房水、玻璃体和神经视网膜中的许多脂质体，精度和准确度高于±20%。此外，我们还证明了该方法在六种不同脂质体同时注射到大鼠玻璃体腔后的药代动力学评估中的体内适用性。我们计算了玻璃体和房水中的药代动力学参数，定量了视网膜中的脂质体浓度，并定量了脂质体在大鼠中的视网膜分布。与单独注射脂质体制剂相比，基于条形码的研究设计使动物数量从 72 只减少到 12 只。我们相信所提出的方法是可靠的，并将减少和完善脂质体和其他基于脂质的系统的眼药代动力学实验。