Transferrin-conjugated polyphosphoester hybrid micelle loading paclitaxel for brain-targeting delivery: synthesis, preparation and in vivo evaluation.

The successful treatment of central nervous system (CNS) disorders is hampered by inefficient drug delivery across the blood-brain barrier (BBB). Transferrin (Tf) could facilitate the transcytosis of coupled nanocarriers through Tf receptor (TfR) mediated pathway. In this study, Tf-modified paclitaxel-loaded polyphosphoester hybrid micells (TPM) was prepared and evaluated for its in vitro and in vivo brain-targeting efficiency. The polyphosphoester hybrid micelle formed a core-shell structure in aqueous solution, and demonstrated high drug entrapping efficiency (89.9±3.4%). In addition, the micelle showed negligible hemolysis even at 2.0 mg/mL. The TPM was 87.85±2.32 nm with ζ potentials -12.33±1.46 mV, and PTX showed sustained release from TPM. TPM demonstrated enhanced cellular uptake and brain accumulation, which were 2 and 1.8-fold of PM, respectively. TPM exhibited strongest anti-glioma activity, and the mean survival time of mice bearing intracranial U-87 MG glioma treated with TPM (39.5 days) was significantly longer than those treated with Taxol® (33.6 days). These results indicated that Tf conjugated micelle could be a promising carrier for brain-targeting drug delivery.