Optimization of the formulation of fe3o4 nanoparticles by box-behnken response surface method and its drug release mechanism in vitro / 中国药学杂志

ABSTRACT

OBJECTIVE: To optimize the formulation of Fe3O4 nanoparticles modified with polyethylene glycol (PEG)through Box-Behnken response surface method.To investigate its release properties in vitro to provide references for the study of drug delivery system. METHODS: Firstly, the formulationof Fe3O4 nanoparticles was optimized by Box-Behnken response surface method. Secondly, the physical and chemical stabilities of Fe3O4 nanoparticles were determined at different stages. Next, doxorubicin hydrochloride, scutellarin and 5-fluorouracil were respectively loaded into Fe3O4 nanoparticles by ultrasonic stirring method and the drug release ability of Fe3O4 nanoparticles was studied by dialysis method. Finally, different mathematical models were applied to fit the release data to explain the release mechanism, and the release ability of Fe3O4 nanoparticles was investigated at different temperatures to clarify the effect of photothermal effect on drug release. RESULTS The particle size of Fe3O4 nanoparticles was from 20 to 30 nm at room temperature. Fe3O4 nanoparticles loading with water-soluble drugs 5-fluorouracil was incompatible with the five models. However, when doxorubicin hydrochloride was loaded, its release fitted well with the Higuchi equation. And both zero-order equation and the Hixson-Crowell equation can match well with such Fe3O4 nanoparticles loading with scutellarin. Finally, it can be clarified with mechanism-verified Ritger-Peppas equation that the simple diffusion motivated the drug release of Fe3O4 nanoparticles loaded with hydrophilic drugs, and the Zero dissolution release mechanism worked when loaded with hydrophobic drugs.As the temperature increases, the release ability of Fe3O4 nanoparticles was increases. CONCLUSION: Hydrophobic drugs can be loaded with SCU in the Fe3O4 nanoparticles by ultrasonic stirring method to improve the biocompatibility of the drugs, which provide some experimental foundation for the research and development of new formulations of poorly soluble drugs.