Biotin-encoded Pullulan-Retinoic Acid Engineered Nanomicelles: Preparation, Optimization and In Vitro Cytotoxicity Assessment in MCF-7 Cells

Biotin and retinoic acid grafted pullulan conjugate was synthesized using carbodiimide activation ester bond formation strategy for biotin targeted delivery of doxorubicin in breast cancer chemotherapy using micelle formulation. The conjugate structure was evaluated and confirmed by proton nuclear magnetic resonance and Fourier transform infrared spectroscopy. Critical micelle concentration of final conjugate was determined using the pyrene fluorescence method. Doxorubicin-loaded micelles were prepared using the direct dissolution method. Physical parameters of optimized micelles comprising particle size, zeta potential, drug loading efficacy, and drug release profile were determined. The results reveal that the nanomicelles have formed with mean particle size of 191 nm and zeta potential of -9.45 mv. The drug loading efficacy of 92% and release efficiency of 81% during 24 h, are also obtained. The structure of the micelles was studied by transition electron microscopy technique. The cytotoxicity of doxorubicin-loaded micelles was studied in MCF-7 cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The results of in vitro cell culture cytotoxicity assay showed that the doxorubicin-loaded biotin grafted retinoic acid-pullulan micelles were more cytotoxic in comparison to the non-targeted pullulan and free doxorubicin.