Clinical Pharmacology Research Center, Ningbo Urinary and Renal Diseases Hospital, Ningbo, China.
Int J Nanomedicine. 2012;7:3547-54. doi: 10.2147/IJN.S32188. Epub 2012 Jul 10.
The aim of this work was to improve oral bioavailability. The uptake of a series of quaternary ammonium salt didodecyl dimethylammonium bromide (DMAB)-modified nanoparticles (with uniform sizes ranging from 50 nm to 300 nm) into heterogeneous human epithelial colorectal adenocarcinoma cells (Caco-2) and human colon adenocarcinoma cells (HT-29) was investigated.
Coumarin-6 (C6) loaded poly (lactide-co-glycolide) (PLGA) nanoparticles were prepared with DMAB using the emulsion solvent diffusion method. The physicochemical properties and cellular uptake of these nanoparticles were studied. Deserno's model was applied to explain the experimental observations.
The results showed that the surface modification of PLGA nanoparticles with DMAB notably improved the cellular uptake. The cellular uptake was size-dependent and had an optimal particle size of 100 nm. The experimental data was integrated numerically, and was in agreement with the theoretical model.
These results indicated that the interactions between the charged nanoparticles and the cells resulted from various forces (eg, electrostatic forces, hydrophobic forces, bending and stretching forces, and limited receptor-mediated endocytosis), and the uptake of the nanoparticles occurred as a result of competition.
本研究旨在提高口服生物利用度。研究了一系列季铵盐双十二烷基二甲基溴化铵(DMAB)修饰的纳米颗粒(粒径均一,范围为 50nm 至 300nm)进入异质人上皮结肠直肠腺癌细胞(Caco-2)和人结肠腺癌细胞(HT-29)的摄取情况。
采用乳化溶剂扩散法,用 DMAB 制备了载香豆素-6(C6)的聚(乳酸-共-乙醇酸)(PLGA)纳米颗粒。研究了这些纳米颗粒的理化性质和细胞摄取情况。应用德雷塞尔(Deserno)模型解释了实验观察结果。
结果表明,DMAB 对 PLGA 纳米颗粒的表面修饰显著提高了细胞摄取。细胞摄取具有尺寸依赖性,最佳粒径为 100nm。对实验数据进行了数值积分,与理论模型一致。
这些结果表明,带电荷的纳米颗粒与细胞之间的相互作用源于各种力(如静电作用力、疏水作用力、弯曲和拉伸作用力以及有限的受体介导的内吞作用),纳米颗粒的摄取是竞争的结果。