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.

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