Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC), Campus Vida, 15782 Santiago de Compostela, Spain.
Department of Cell Biology and Histology, Faculty of Medicine and Odontology, University of Basque Country, B° Sarriena, s/n, 48940 Leioa, Spain.
Eur J Pharm Biopharm. 2018 Apr;125:85-94. doi: 10.1016/j.ejpb.2018.01.009. Epub 2018 Jan 19.
Glycosaminoglycans (GAGs) are natural polymers that are broadly used in gene delivery systems to increase stability as well as decrease toxicity and nonspecific interactions, thereby increasing transfection efficiency. In this work, we propose sorbitan ester-based lipid nanoparticles (SENS) functionalised with the GAGs chondroitin sulfate (CS) and hyaluronic acid (HA) as gene delivery systems. For this purpose, we describe the design and evaluation of these nanosystems loaded with plasmid DNA, including an evaluation of their physicochemical characteristics, stability properties, ability to protect and efficiently transfect cells with Enhanced Green Fluorescent Protein plasmid (pEGFP) in vitro, and biocompatibility both in vitro and in vivo. We confirm that molecules with high biological value and targeting potential, such as HA and CS, can be successfully incorporated into our recently developed sorbitan ester-based nanoparticles (SENS) and that this incorporation leads to effective stabilisation of both nanosystems as well as protects plasmid DNA. We demonstrated that the aforementioned incorporation of HA and CS enables long-term stability of the nanosystems in both liquid and lyophilised states, which is a remarkable property that can aid in their transfer to industry. The ability of these functionalised nanosystems to transfect the A549 cell line without compromising cell viability was also shown, as well as their innocuous safety profile in vivo. Thus, we provide valuable evidence of the suitable properties and potential of these hybrid nanoparticles as gene delivery systems.
糖胺聚糖（GAGs）是广泛用于基因传递系统的天然聚合物，可提高稳定性、降低毒性和非特异性相互作用，从而提高转染效率。在这项工作中，我们提出了基于山梨糖醇酯的脂质纳米颗粒（SENS），其表面功能化有糖胺聚糖硫酸软骨素（CS）和透明质酸（HA），作为基因传递系统。为此，我们描述了这些载有质粒 DNA 的纳米系统的设计和评估，包括对其物理化学特性、稳定性、保护和有效转染体外带增强型绿色荧光蛋白质粒（pEGFP）的能力以及体外和体内的生物相容性进行评估。我们证实，具有高生物价值和靶向潜力的分子，如 HA 和 CS，可以成功地整合到我们最近开发的基于山梨糖醇酯的纳米颗粒（SENS）中，并且这种整合导致纳米系统的有效稳定化，并保护质粒 DNA。我们表明，上述 HA 和 CS 的掺入使得纳米系统在液体和冻干状态下都具有长期稳定性，这是一个显著的特性，可以帮助它们向工业转移。这些功能化纳米系统在不影响细胞活力的情况下转染 A549 细胞系的能力，以及它们在体内的无害安全特性也得到了证明。因此，我们为这些杂化纳米颗粒作为基因传递系统的合适特性和潜力提供了有价值的证据。
