Czerniel Joanna, Gostyńska-Stawna Aleksandra, Sommerfeld-Klatta Karina, Przybylski Tomasz, Krajka-Kuźniak Violetta, Stawny Maciej
Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland.
Department of Toxicology, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland.
Pharmaceutics. 2025 Apr 8;17(4):493. doi: 10.3390/pharmaceutics17040493.
Parenteral nutrition (PN) is a lifesaving therapeutic approach for patients unable to meet nutritional needs through oral or enteral routes. Lipid nanoemulsions (NEs), a critical component of PN, provide essential fatty acids and influence the formulation's physicochemical properties. Advances in drug delivery systems have led to novel intravenous NEs with improved stability, purity, or ability for nutrient/active substance delivery. Due to scattered information and the lack of a standardized protocol for testing intravenous lipid NEs, this study aimed to develop a robust assessment method. The protocol focuses on characterizing the physicochemical properties, stability, and biological efficacy of novel NEs while adhering to bioethical standards. Four NEs were formulated based on fatty acid profile analysis, and to demonstrate the applicability of our protocol, each NE utilized a distinct emulsifier system. A comprehensive in vitro assessment protocol integrating multiple analytical techniques was employed to evaluate their performance. The mean droplet diameter (MDD) of developed NEs ranged from 180.7 to 185.9 nm, significantly smaller than commercial formulations (249.6-335.4 nm). PFAT5 remained below 0.02%, except for ILE-HS (0.12%), and the zeta potential (ZP) was below -29.8 mV. The freeze-thaw stability constant (K) of developed NEs was in the range of commercial formulation, and the sterilization stability constant (K) was below 10, except for ILE-HS (23.61 ± 1.65). Injectability tests confirmed that ILE-ELP and ILE-T could be infused at 50 mL/h using an intravenous access with a minimum diameter of 21 G. Hemolytic activity met the strictest criteria (<5%), and MTT assays showed higher cell viability at low concentrations for all NEs except ILE-ELP. The developed five-step protocol provides a unified framework for assessing intravenous lipid NEs, allowing for the selection of NEs with the highest potential for further in vivo assessment.
肠外营养（PN）是一种为无法通过口服或肠内途径满足营养需求的患者提供救命的治疗方法。脂质纳米乳剂（NEs）是PN的关键组成部分，可提供必需脂肪酸并影响制剂的物理化学性质。药物递送系统的进展已导致具有改善的稳定性、纯度或营养物质/活性物质递送能力的新型静脉内NEs。由于信息分散且缺乏测试静脉内脂质NEs的标准化方案，本研究旨在开发一种可靠的评估方法。该方案侧重于表征新型NEs的物理化学性质、稳定性和生物学功效，同时遵守生物伦理标准。基于脂肪酸谱分析制备了四种NEs，为证明我们方案的适用性，每种NEs都采用了不同的乳化剂系统。采用综合多种分析技术的全面体外评估方案来评估它们的性能。所制备NEs的平均液滴直径（MDD）在180.7至185.9nm之间，明显小于市售制剂（249.6 - 335.4nm）。除了ILE - HS（0.12%）外，PFAT5均低于0.02%，且zeta电位（ZP）低于 - 29.8mV。所制备NEs的冻融稳定性常数（K）在市售制剂范围内，除了ILE - HS（23.61±1.65）外，灭菌稳定性常数（K）低于10。注射性测试证实，使用最小直径为21G的静脉通路，ILE - ELP和ILE - T可以以50mL/h的速度输注。溶血活性符合最严格的标准（<5%），MTT分析表明，除ILE - ELP外，所有NEs在低浓度下均具有较高的细胞活力。所开发的五步方案为评估静脉内脂质NEs提供了一个统一的框架，允许选择具有最高潜力进行进一步体内评估的NEs。
