Cellular uptake and transport characteristics of chitosan modified nanoparticles in Caco-2 cell monolayers.

The bioadhesive drug delivery systems, chitosan modified nanoparticles, can efficiently adhere to mucosal surface of gastrointestinal tract and prolong residence time but a deeper understanding about its cellular uptake and transport is still lack. Hence, the present study was designed to compare the process of uptake and transport between chitosan modified and unmodified PLGA nanoparticles. Chitosan modified nanoparticles were formulated by classic and chemical methods. The morphology and modification potency were characterized by zeta potential, FTIR, DSC, XPS and TEM. Coumarin-6 load chitosan modified nanoparticles were incubated with Caco-2 cells to study the process of uptake and transport. The kinetic of cellular uptake for chitosan modified and unmodified nanoparticles was time- and concentration-dependent endocytosis but the cellular uptake efficiency of modified nanoparticles was significantly higher than that of unmodified one within the high concentration range (25.0-100.0 µg/mL). The modified nanoparticles underwent clathrin-mediated endocytosis and macropinocytosis but unmodified nanoparticles occurred a clathrin-mediated endocytosis. Both types of nanoparticles can increase caulophine with low solubility and poor stability transmembrane transport and the modified nanoparticles exhibited a better transcellular permeability. Therefore, the chitosan modified nanoparticles showed significantly improved cellular uptake and transcellular transport and a potential improvement in the efficacy of oral drug delivery.

Homing in on an intracellular target for delivery of loaded nanoparticles functionalized with a histone deacetylase inhibitor.

Functionalized nanoparticles (NPs) are usually used to enhance cellular penetration for targeted drug delivery that can improve efficacy and reduce side effects. However, it is difficult to exploit intracellular targets for similar delivery applications. Herein we describe the targeted delivery of functionalized NPs by homing in on an intracellular target, histone deacetylases (HDACs). Specifically, a modified poly-lactide-co-glycolideacid (FPLGA) was yielded by conjugation with an HDAC inhibitor. Subsequently, FPLGA was used to prepare functionalized FPLGA NPs. Compared to unmodified NPs, FPLGA NPs were more efficiently uptaken or retained by MCF-7 cells and showed longer retention time intracellular. In vivo fluorescence imaging also revealed that they had a higher accumulation and a slower elimination than unmodified NPs. FPLGA NPs loaded with paclitaxel exhibited superior anticancer efficacy compared with unmodified NPs. These results offer a promising approach for intracellular drug delivery through elevating the concentration of NPs.