Đoković Jelena B, Demisli Sotiria, Savić Sanela M, Marković Bojan D, Cekić Nebojša D, Randjelovic Danijela V, Mitrović Jelena R, Lunter Dominique Jasmin, Papadimitriou Vassiliki, Xenakis Aristotelis, Savić Snežana D
Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece.
Pharmaceutics. 2022 Aug 10;14(8):1666. doi: 10.3390/pharmaceutics14081666.
A nanotechnology-based approach to drug delivery presents one of the biggest trends in biomedical science that can provide increased active concentration, bioavailability, and safety compared to conventional drug-delivery systems. Nanoemulsions stand out amongst other nanocarriers for being biodegradable, biocompatible, and relatively easy to manufacture. For improved drug-delivery properties, longer circulation for the nanoemulsion droplets should be provided, to allow the active to reach the target site. One of the strategies used for this purpose is PEGylation. The aim of this research was assessing the impact of the oil phase selection, soybean or fish oil mixtures with medium chain triglycerides, on the physicochemical characteristics and injectability of curcumin-loaded PEGylated nanoemulsions. Electron paramagnetic resonance spectroscopy demonstrated the structural impact of the oil phase on the stabilizing layer of nanoemulsions, with a more pronounced stabilizing effect of curcumin observed in the fish oil nanoemulsion compared to the soybean oil one. The design of the experiment study, employed to simultaneously assess the impact of the oil phase, different PEGylated phospholipids and their concentrations, as well as the presence of curcumin, showed that not only the investigated factors alone, but also their interactions, had a significant influence on the critical quality attributes of the PEGylated nanoemulsions. Detailed physicochemical characterization of the NEs found all formulations were appropriate for parenteral administration and remained stable during two years of storage, with the preserved antioxidant activity demonstrated by DPPH and FRAP assays. In vitro release studies showed a more pronounced release of curcumin from the fish oil NEs compared to that from the soybean oil ones. The innovative in vitro injectability assessment, designed to mimic intravenous application, proved that all formulations tested in selected experimental setting could be employed in prospective in vivo studies. Overall, the current study shows the importance of oil phase selection when formulating PEGylated nanoemulsions.
基于纳米技术的药物递送方法是生物医学科学中最大的趋势之一，与传统药物递送系统相比，它可以提高活性成分浓度、生物利用度和安全性。纳米乳剂在其他纳米载体中脱颖而出，因为它具有可生物降解、生物相容性好且相对易于制造的特点。为了改善药物递送性能，应使纳米乳剂液滴具有更长的循环时间，以便活性成分能够到达靶位点。用于此目的的策略之一是聚乙二醇化。本研究的目的是评估油相选择（大豆油或鱼油与中链甘油三酯的混合物）对负载姜黄素的聚乙二醇化纳米乳剂的理化特性和可注射性的影响。电子顺磁共振光谱证明了油相对纳米乳剂稳定层的结构影响，与大豆油纳米乳剂相比，在鱼油纳米乳剂中观察到姜黄素具有更明显的稳定作用。实验研究设计用于同时评估油相、不同聚乙二醇化磷脂及其浓度以及姜黄素的存在的影响，结果表明，不仅所研究的因素本身，而且它们之间的相互作用，都对聚乙二醇化纳米乳剂的关键质量属性有显著影响。对纳米乳剂的详细理化表征发现，所有制剂都适合肠胃外给药，并且在两年的储存期间保持稳定，通过DPPH和FRAP测定证明其抗氧化活性得以保留。体外释放研究表明，与大豆油纳米乳剂相比，鱼油纳米乳剂中姜黄素的释放更为明显。旨在模拟静脉内应用的创新体外可注射性评估证明，在选定实验环境中测试的所有制剂都可用于未来的体内研究。总体而言，当前研究表明了在制备聚乙二醇化纳米乳剂时油相选择的重要性。
