Oral administration of pH-responsive polyamine modified cyclodextrin nanoparticles for controlled release of anti-tumor drugs

Abstract

pH-responsive nanoparticles based on polyamine modified β-cyclodextrin (PEHA-β-CD) and sodium dodecylbenzene sulfonate (SDBS) were fabricated through electrostatic interaction and employed to load doxorubicin (DOX) and celastrol (CSL) in the form of DOX(CSL)-loaded PEHA-β-CD/SDBS. The obtained nanoparticles were characterized using Tyndall effect, UV–vis, XRD, 1H NMR, DLS, TEM and zeta potential. The DOX(CSL)-loaded PEHA-β-CD/SDBS with minimal amount released in the acidic pH environment (pH = 1.2) like that of the stomach, while effective release in the basic pH environment (pH = 8.5) like that of the intestine. The release kinetics were investigated using different models to explain drug release mechanism. The pH-controlled release nanoparticles system provides an opportunity to the oral route of drug administration. The Methyl Thiazol Tetrazolium (MTT) assay indicated that DOX(CSL)-loaded PEHA-β-CD/SDBS showed high toxicity to five tumor cells. What's more, it exhibited low cytotoxicity to normal BEAS-2B epithelial cells. The flow cytometry analysis showed that DOX(CSL)-loaded PEHA-β-CD/SDBS could inhibit tumor cells growth through inducing cells apoptosis. These results indicated that the pH-responsive nanoparticles held a great promise to be developed as an oral administration drugs delivery system with sustained release and target specificity.