Abstract

To prepare polyethylene glycol (PEG)-coated, muco-inert nanoparticles, we investigated the interaction between nanoparticles and mucin, and analyzed the cellular uptake of nanoparticles in HGC-27 cells, which are a mucin-producing, gastric cancer cell line. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were manufactured through a nanoprecipitation/emulsion evaporation technique, and coumarin-6 was encapsulated as a fluorescent marker. We characterized and evaluated the nanoparticles. We examined the cellular uptake of PLGA nanoparticles in HGC-27 cells with confocal laser scanning microscopy and flow cytometry. Nanoparticles prepared using a nanoprecipitation method were 120-150 nm in size, while nanoparticles prepared using an emulsion evaporation method were 400-450 nm in size. EE% of coumarin-6 in the nanoparticles was more than 80%. The anti-adhesive ability of nanoparticles to pig-gastric mucin (PM) was notably affected by PEG coating-density, 10% PEG2000-PLGA nanoparticles and 15% PEG2000-PLGA nanoparticles possessed the strongest resistance to PM. However, the PLGA nanoparticles were strong while the chitosan-loaded nanoparticles were very weak. Our results from both confocal laser scanning microscopy as well as flow cytometry showed that mPEG-PLGA-NPs are rapidly uptaken by mucin-producing HGC-27 cells. The number of 10% mPEG-PLGA-NPs taken up by cells was 1.6- to 2.1-fold higher than PLGA-NPs incubated for the same amount of time. In conclusion, mPEG-PLGA-NPs possess hydrophilic and near-neutrally-charged surfaces that minimize mucoadhesion by reducing hydrophobic or electrostatic interactions. Both the low-PEG MW and the high density of PEG surface coverage are critical for the uptake of mPEG-PLGA-NPs in HGC-27 cells. At the same time, the size of nanoparticles was also very important.

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