Biocompatibility, cellular uptake and biodistribution of the polymeric amphiphilic nanoparticles as oral drug carriers

Oleoyl-carboxymethyl-chitosan (OCMCS) was synthesized and were soluble at neutral pH. The critical micelle concentration (CMC) of OCMCS in deionized water was 0.021 mg/ml. OCMCS nanoparticles were successfully prepared via self-assembly with mean diameter of 215.34 nm, zeta potential of 19.26 mV and an almost spherical shape as determined by electron microscopy. The OCMCS nanoparticles showed low erythrocyte membrane-damaging effect. The MTT survival assay indicated no significant cytotoxicity to Caco-2 cells and MEFs cells. The uptake of FITC labeled OCMCS nanoparticles by Caco-2 cells was confirmed via confocal laser scanning microscope (CLSM). In vivo toxicity assays were performed via histopathological evaluation, and no specific anatomical pathological changes or tissue damage was observed in the tissues of carps. The extent of tissue distribution and retention following oral administration of FITC-OCMCS nanoparticles was analyzed for 3 days. After 3 days, the nanoparticles remained detectable in the muscle, heart, kidney, liver, intestine, and spleen. The results showed that 34.32% of the particles were localized in the liver, 18.79% in the kidney, and 17.36% in the heart. The lowest percentage was observed in the muscle. These results implied that OCMCS nanoparticles had great potential to be applied as safe carriers for the oral administration of protein drugs.

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► The OCMCS nanoparticles showed low erythrocyte membrane-damaging effect.
► The MTT survival assay indicated no significant cytotoxicity.
► The uptake of FITC labeled OCMCS nanoparticles by Caco-2 cells was confirmed by CLSM.
► The in vivo toxicity study demonstrated the safety of OCMCS nanoparticles.
► FITC-OCMCS nanoparticles were detected in some tissues after oral delivery to carp.