Department of Pharmaceutical Technology, Medical University of Gdansk, al. gen. J. Hallera 107, 80-416 Gdansk, Poland.
Department of Pharmaceutical Technology, Medical University of Gdansk, al. gen. J. Hallera 107, 80-416 Gdansk, Poland.
Eur J Pharm Sci. 2019 Jan 15;127:92-101. doi: 10.1016/j.ejps.2018.10.018. Epub 2018 Oct 17.
Lecithin and isolated phospholipids (mainly phosphatidylcholine) have been used for years as pharmaceutical excipients in parenteral formulations: submicron emulsions, liposomes and mixed micelles. Under development are also other lecithin-based drug delivery systems, e.g. aqueous lecithin dispersions (WLDs). The aim of the study was to investigate the properties and potential cytotoxicity of 7 different phospholipid-based dispersions intended for parenteral administration: emulsions, liposomes and WLDs. Each formulation contained egg phosphatidylcholine (PC) in the concentration range of 0.6-5.0%, and to some formulations other surfactants, such as polysorbate 80 (P80), Solutol HS 15 (HS) and cholesterol (Ch) were added. Particles in all dispersions were homogenous (PDI < 0.26) and submicron in size (Z-average in the range of approx. 100-260 nm). The cytotoxicity of all tested formulations was evaluated by means of 3 independent methods: a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, a real-time xCELLigence (RTCA) system, and a flow cytometry analysis, using two cell lines: human embryonic kidney 293 (HEK-293) and human promyelocytic leukaemia (HL-60). The results indicated that regardless of the test method and cell line type, the cytotoxicity of all formulations was low, especially when dispersions diluted to concentrations of =10% were tested. A more pronounced cytotoxic effect was noticed only for the following formulations: E-P80 (emulsion containing P80), WLD (unbuffered aqueous lecithin dispersion) and L-Ch (liposomes containing Ch), tested as less diluted (concentration 10% or 25%). IC50 values measured for these dispersions (on HL-60 cells) amounted to: 10.4 ± 0.5% (v/v), 14.4 ± 0.2% (v/v) and 24.2 ± 0.6% (v/v), respectively. Our investigation confirmed the biocompatibility of all tested phospholipid-based formulations: emulsions, liposomes and also newly-developed WLDs, which can be considered as safe parenteral drug carriers.
多年来，卵磷脂和分离的磷脂（主要是磷脂酰胆碱）一直被用作注射制剂的药用辅料：亚微米乳液、脂质体和混合胶束。正在开发的其他基于卵磷脂的药物传递系统，例如水性卵磷脂分散体（WLD）。本研究的目的是研究 7 种不同的用于注射给药的基于磷脂的分散体的特性和潜在细胞毒性：乳液、脂质体和 WLD。每种制剂均含有浓度为 0.6-5.0%的蛋黄卵磷脂（PC），并向某些制剂中添加了其他表面活性剂，如聚山梨酯 80（P80）、Solutol HS 15（HS）和胆固醇（Ch）。所有分散体中的颗粒均均匀（PDI<0.26）且粒径为亚微米级（Z-平均粒径在约 100-260nm 范围内）。通过 3 种独立的方法评估所有测试制剂的细胞毒性：3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）测定法、实时 xCELLigence（RTCA）系统和流式细胞术分析，使用两种细胞系：人胚肾 293（HEK-293）和人早幼粒细胞白血病（HL-60）。结果表明，无论测试方法和细胞系类型如何，所有制剂的细胞毒性均较低，尤其是在将制剂稀释至=10%的浓度进行测试时。仅当以下制剂以较低的稀释度（浓度为 10%或 25%）进行测试时，才会发现更明显的细胞毒性作用：E-P80（含有 P80 的乳液）、WLD（无缓冲水性卵磷脂分散体）和 L-Ch（含有 Ch 的脂质体）。对于这些分散体（在 HL-60 细胞上）测量的 IC50 值分别为：10.4±0.5%（v/v）、14.4±0.2%（v/v）和 24.2±0.6%（v/v）。我们的研究证实了所有测试的基于磷脂的制剂的生物相容性：乳液、脂质体以及新开发的 WLD，它们可被视为安全的注射用药物载体。
