Thin-film hydration preparation method and stability test of DOX-loaded disulfide-linked polyethylene glycol 5000-lysine-di-tocopherol succinate nanomicelles

Abstract

A novel redox-responsive PEG-sheddable copolymer of disulfide-linked polyethylene glycol 5000-lysine-di-tocopherol succinate (P5kSSLV) was designed and synthesized. Thin-film hydration method was used to prepare DOX-loaded P5kSSLV nanomicelle. To optimize the preparation technology, we investigate the effects of dosage, type of organic solvent, hydration temperature and time, and cryoprotectant on drug-loading content, encapsulation efficiency, particle size, and zeta potential. The mean particle size and zeta potential were determined by Zetasizer. The morphology of the P5kSSLV-DOX nanomicelles was visualized by transmission electron microscopy. The drug-loading content and encapsulation efficiency of P5kSSLV-DOX nanomicelle were investigated by UV. The drug-loading content, encapsulation efficiency, particle size, and zeta potential of the final optimized nanomicelles were 4.58%, 97.20%, 30.21nm and -0.84mV, respectively. In addition, the stability of nanomicelles was investigated, which included dilution stability and storage stability. The results showed that P5kSSLV-DOX nanomicelle had good dilution stability and storage stability at 4°C. The preparation method of P5kSSLV-DOX nanomicelle with thin-film hydration method was practical and simple, which was valuable to be further studied.