Stimuli-responsive zein-based nanoparticles as a potential carrier for ellipticine: Synthesis, release, and in vitro delivery

In the present research, we have investigated a drug delivery system based on the pH-responsive behaviors of zein colloidal nanoparticles coated with sodium caseinate (SC) and poly ethylene imine (PEI). These systematically designed nanoparticles were used as nanocarriers for encapsulation of ellipticine (EPT), as an anticancer drug. SC and PEI coatings were applied through electrostatic adsorption, leading to the increased size and improved polydispersity index of nanoparticles as well as sustained release of drug. Physicochemical characteristics such as hydrodynamic diameter, size distribution, zeta potential and morphology of nanoparticles prepared using different formulations and conditions were also determined. Based on the results, EPT was encapsulated into the prepared nanoparticles with a high drug loading capacity (5.06%) and encapsulation efficiency (94.8%) under optimal conditions. in vitro experiments demonstrated that the release of EPT from zein-based nanoparticles was pH sensitive. When the pH level decreased from 7.4 to 5.5, the rate of drug release was considerably enhanced. The mechanism of pH-responsive complexation in the drug encapsulation and release processes was extensively investigated. The pH-dependent electrostatic interactions and drug state were hypothesized to affect the release profiles. Compared to the EPT-loaded zein/PEI nanoparticles, the EPT-loaded zein/SC nanoparticles exhibited a better drug sustained-release profile, with a smaller initial burst release and longer release period. According to the results of in vitro cytotoxicity experiments, drug-free nanoparticles were associated with a negligible cytotoxicity, whereas the EPT-loaded nanoparticles displayed a high toxicity for the cancer cell line, A549. Our findings indicate that these pH-sensitive protein-based nanoparticles can be used as novel nanotherapeutic tools and potential antineoplastic drug carriers for cancer chemotherapy with controlled release.