Preparation and characterization of shell cross-linked PLGA nanoparticles with pH-responsiveness for drug delivery

To obtain the shell cross-linked PLGA-NPs (PCV-NPs), PLGA nanoparticles (PNPs) were prepared by emulsification technique first. Subsequently, chitosan was coated on the surface of the PLGA-NPs via the electrostatic interaction. Finally, vanillin, a non-toxic chemical cross-linker, was chosen to react with the chitosan to form Schiff base on the surface of nanoparticles. Size and zeta potential of PCV-NPs detected by Malvern Zetasizer Nano ZS90 were in the range of (277.60 ± 38.01 ) nm and (21.60 ± 4.51) mV, respectively. Besides, SEM images show PCV-NPs have smooth and spherical morphology. Infrared spectroscopy was used to detect the chemical structure of all the NPs, and the characteristic vibrating peak of the Schiff base at 1640 cm^-1 emerged on the spectral line of PCV-NPs. PCV-NPs performed excellent stability within 24 h incubation in the serum containing medium. The cellular uptake study was performed using hydrophobic fluorescein coumarin 6, the results indicated coumarin 6-loaded PCV-NPs possessed better transmembrane transport capacity compared with P-NPs. And the cytotoxicity studies demonstrated that there was no obvious cytotoxicity of blank PCV-NPs. Furthermore, docetaxel, a model drug, was encapsulated into PCV-NPs with high drug loading (7.48%) and entrapment efficiency (34.98%). In addition, the DTX cumulative release of DTX-loaded PCV-NPs was 58.66% after 90 h of incubation at pH 5.0. In comparison, the drug release was reduced to 50.63% at pH 7.4. DTX-loaded PCV-NPs showed efficient cell killing ability after 48 h incubation with A549 cells, the IC₅₀ value of which was 0.0009 μg/mL.