Inserm, LIRIC - UMR 995, F-59 000 Lille, France; Univ Lille, LIRIC - UMR 995, F-59 045 Lille, France; CHRU de Lille, LIRIC - UMR 995, F-59 000 Lille, France.
Inserm, LIRIC - UMR 995, F-59 000 Lille, France; Univ Lille, LIRIC - UMR 995, F-59 045 Lille, France; CHRU de Lille, LIRIC - UMR 995, F-59 000 Lille, France.
Int J Pharm. 2018 Oct 25;550(1-2):316-324. doi: 10.1016/j.ijpharm.2018.08.054. Epub 2018 Aug 29.
Different types of biodegradable nanoparticles (NP) have been studied as nasal mucosa cell delivery systems. These nanoparticles need to strongly interact with mucosa cells to deliver their payload. However, only a few simultaneous comparisons have been made and it is therefore difficult to determine the best candidate. Here we compared 5 types of nanoparticles with different surface charge (anionic or cationic) and various inner compositions as potential vectors: cationic and anionic liposomes, cationic and anionic PLGA (Poly Lactic co-Glycolic Acid) NP and porous and cationic maltodextrin NP (cationic surface with an anionic lipid core: NPL). We first quantified their nasal residence time after nasal administration in mice using in vivo live imaging and NPL showed the longest residence time. In vitro endocytosis on mucosal cells (airway epithelial cells, macrophages and dendritic cells) using labeled nanoparticles were performed by flow cytometry and confocal microscopy. Among the 5 nanoparticles, NPL were taken up to the greatest extent by the 3 different cell lines and the endocytosis mechanisms were characterized. Taken together, we observed that the nanoparticles' cationic surface charge is insufficient to improve mucosal residence time and cellular uptake and that the NPL are the best candidates to interact with airway mucosal cells.
不同类型的可生物降解纳米颗粒 (NP) 已被研究作为鼻腔黏膜细胞的递药系统。这些纳米颗粒需要与黏膜细胞强烈相互作用才能传递其有效载荷。然而,只有少数同时比较被进行,因此很难确定最佳的候选物。在这里,我们比较了 5 种具有不同表面电荷(阴离子或阳离子)和不同内部组成的纳米颗粒作为潜在载体:阳离子和阴离子脂质体、阳离子和阴离子 PLGA(聚乳酸-共-羟基乙酸)纳米颗粒和多孔阳离子麦芽糊精纳米颗粒(阳离子表面带有阴离子脂质核心:NPL)。我们首先使用体内活体成像技术在小鼠中定量评估了这 5 种纳米颗粒经鼻腔给药后的鼻腔驻留时间,结果表明 NPL 的鼻腔驻留时间最长。使用标记的纳米颗粒通过流式细胞术和共聚焦显微镜在黏膜细胞(气道上皮细胞、巨噬细胞和树突状细胞)上进行体外内吞作用。在这 5 种纳米颗粒中,NPL 被 3 种不同的细胞系摄取的程度最大,并对其内化机制进行了表征。综上所述,我们观察到纳米颗粒的阳离子表面电荷不足以改善黏膜的驻留时间和细胞摄取,而 NPL 是与气道黏膜细胞相互作用的最佳候选物。