Botto Chiara, Mauro Nicolò, Amore Erika, Martorana Elisabetta, Giammona Gaetano, Bondì Maria Luisa
Laboratorio di Polimeri Biocompatibili, Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
Istituto per lo Studio dei Materiali Nanostrutturati (ISMN), CNR, U.O.S. Palermo, via Ugo La Malfa, 153, 90146 Palermo, Italy.
Int J Pharm. 2017 Jan 10;516(1-2):334-341. doi: 10.1016/j.ijpharm.2016.11.052. Epub 2016 Nov 23.
Solid lipid nanoparticles (SLNs) may be considered as a new approach for therapeutics for many diseases. In addition to drug delivery, their use as non-viral vectors for gene delivery can be obtained by including cationic lipids, which provide a positive surface potential that favors binding to the nucleic acids as DNA, siRNA, miRNA, etc. In fact, the addition of cationic surfactants is indispensable for obtaining nanoparticles with surface positive charge. In this study, three different cationic lipids (dioctadecyl dimethyl ammonium bromide, cetyltrimethyl ammonium bromide, cetylpyridinium chloride) and Brij 76 as nonionic surfactant were employed to formulate Precirol ATO 5 based cSLN using pEGFP-LUC as model plasmid. The physicochemical properties of cSLN were influenced by both type and amount of surfactants. Thermal analyses of bulk cSLN showed endothermic peaks significantly different from the ones of the single pure components, hinting a complete entanglement of the lipid matrix with the surfactants and justifying the different behavior of the cSLN in the ability to interact with the plasmid DNA. Finally, the biocompatibility of cSLN was demonstrated by hemolytic assays. These results may give an insight into the choice of surfactants in order to obtain non-toxic and highly effective delivery systems for gene therapy.
固体脂质纳米粒（SLNs）可被视为治疗多种疾病的一种新方法。除了药物递送外，通过加入阳离子脂质可使其用作基因递送的非病毒载体，阳离子脂质可提供正表面电位，有利于与DNA、siRNA、miRNA等核酸结合。事实上，添加阳离子表面活性剂对于获得具有表面正电荷的纳米粒是必不可少的。在本研究中，使用三种不同的阳离子脂质（二辛基二甲基溴化铵、十六烷基三甲基溴化铵、十六烷基吡啶氯化物）和作为非离子表面活性剂的Brij 76，以pEGFP-LUC为模型质粒来制备基于Precirol ATO 5的阳离子固体脂质纳米粒（cSLN）。cSLN的物理化学性质受表面活性剂的类型和用量影响。大量cSLN的热分析显示吸热峰与单一纯组分的吸热峰显著不同，这表明脂质基质与表面活性剂完全缠结，并解释了cSLN在与质粒DNA相互作用能力方面的不同行为。最后，通过溶血试验证明了cSLN的生物相容性。这些结果可能有助于深入了解表面活性剂的选择，以便获得用于基因治疗的无毒且高效的递送系统。
