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Xu A.,Clinical Pharmacology Research Center | Yao M.,Zhejiang University | Xu G.,Tsinghua University | Ying J.,Clinical Pharmacology Research Center | And 3 more authors.
International Journal of Nanomedicine | Year: 2012

Background: 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. © 2012 Xu et al, publisher and licensee Dove Medical Press Ltd. Source

Ma W.,Clinical Pharmacology Research Center | Xu A.,Clinical Pharmacology Research Center | Ying J.,Clinical Pharmacology Research Center | Li B.,Zhejiang University | Jin Y.,Zhejiang University
Journal of Biomedical Nanotechnology | Year: 2015

In the present study, we developed novel core-shell-type lipid/particle assemblies comprising poly(lactic-co-glycolic acid) nanoparticle cores coated with a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine shell. Hydrophobic dihydroartemisinin and hydrophilic doxorubicin were co-loaded in the core-shell-type lipid/particle assemblies for combination chemotherapy. The physicochemical properties of the dual drug-loaded core-shell-type lipid/particle assemblies were characterized. The results of colorimetric cell viability assay and cellular uptake experiments demonstrated that the lipid/particle hybrid could increase the accumulation of doxorubicin accumulation in cell nuclei, thus enhancing cell cytotoxicity. This effect contributed to the high treatment efficiency of dihydroartemisinin and doxorubicin. These biodegradable lipid/polymer hybrid particles could be promising delivery systems to improve combination chemotherapy. Copyright © 2015 American Scientific Publishers. All rights reserved. Source

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