Reading School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6AD, United Kingdom.
School of Pharmacy, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, United Kingdom.
Eur J Pharm Sci. 2018 Sep 15;122:230-238. doi: 10.1016/j.ejps.2018.06.032. Epub 2018 Jun 30.
In this study, we synthesised thiolated silica nanoparticles using 3-mercaptopropyltrimethoxysilane and functionalised them with either 5 kDa methoxy polyethylene glycol maleimide (PEG) or 5 kDa alkyne-terminated poly(2-ethyl-2-oxazoline) (POZ). The main objectives of this study are to investigate the effects of pH on the size and ξ-potential of these nanoparticles and evaluate their mucoadhesive properties ex vivo using rat intestinal mucosa. The sizes of thiolated, PEGylated and POZylated silica nanoparticles were 53 ± 1, 68 ± 1 and 59 ± 1 nm, respectively. The size of both thiolated and POZylated nanoparticles significantly increased at pH ≤ 2, whereas no size change was observed at pH 2.5-9 for both these two types of nanoparticles. On the other hand, the size of PEGylated nanoparticles did not change over the studied pH range (1.5-9). Moreover, thiolated nanoparticles were more mucoadhesive in the rat small intestine than both PEGylated and POZylated nanoparticles. After 12 cycles of washing (with a total of 20 mL of phosphate buffer solution pH 6.8), a significantly greater amount of thiolated nanoparticles remained on the intestinal mucosa than FITC-dextran (non-mucoadhesive polymer, p < 0.005) and both PEGylated and POZylated nanoparticles (p < 0.05 both). However, both PEGylated and POZylated nanoparticles showed similar retention to FITC-dextran (p > 0.1 for both). Thus, this study indicates that thiolated nanoparticles are mucoadhesive, whereas PEGylated and POZylated nanoparticles are non-mucoadhesive in the ex vivo rat intestinal mucosa model. Each of these nanoparticles has potential applications in mucosal drug delivery.
在这项研究中，我们使用 3-巯基丙基三甲氧基硅烷合成了巯基化硅纳米粒子，并分别用 5kDa 甲氧基聚乙二醇马来酰亚胺（PEG）或 5kDa 炔基封端聚（2-乙基-2-恶唑啉）（POZ）对其进行功能化。本研究的主要目的是研究 pH 值对这些纳米粒子粒径和ξ-电位的影响，并使用大鼠肠黏膜评估其体外黏膜黏附性能。巯基化、PEG 化和 POZ 化硅纳米粒子的粒径分别为 53±1、68±1 和 59±1nm。巯基化和 POZ 化纳米粒子的粒径在 pH≤2 时显著增加，而这两种纳米粒子在 pH 2.5-9 时粒径没有变化。另一方面，PEG 化纳米粒子的粒径在研究的 pH 范围内（1.5-9）没有变化。此外，与 PEG 化和 POZ 化纳米粒子相比，巯基化纳米粒子在大鼠小肠中的黏附性更强。经过 12 次（共 20mL 磷酸盐缓冲液 pH 6.8）洗涤循环后，与非黏附性聚合物 FITC-葡聚糖（p<0.005）以及 PEG 化和 POZ 化纳米粒子（p<0.05 均）相比，更多的巯基化纳米粒子留在肠黏膜上。然而，PEG 化和 POZ 化纳米粒子与 FITC-葡聚糖的保留率相似（两者均 p>0.1）。因此，本研究表明，在体外大鼠肠黏膜模型中，巯基化纳米粒子具有黏附性，而 PEG 化和 POZ 化纳米粒子则不具有黏附性。这些纳米粒子中的每一种都有可能在黏膜药物传递中得到应用。
