A physical model for the size-dependent cellular uptake of nanoparticles modified with cationic surfactants

Abstract

Airen Xu,1,* Mingfei Yao,2,* Guangkui Xu,3 Jingyan Ying,1 Weicheng Ma,1 Bo Li,2 Yi Jin21Clinical Pharmacology Research Center, Ningbo Urinary and Renal Diseases Hospital, Ningbo, 2College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 3Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing, China *These authors contributed equally to this workBackground: 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.Methods: 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.Results: 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.Conclusion: 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.Keywords: coumarin-6, nanoparticles, cellular uptake, Deserno’s model