Folic acid modified TPGS as a novel nano-micelle for delivery of nitidine chloride to improve apoptosis induction in Huh7 human hepatocellular carcinoma

Background: The development of novel and effective drugs for targeted human hepatocellular carcinoma still remains a great challenge. The alkaloid nitidine chloride (NC), a component of a traditional Chinese medicine, has been shown to have Anticancer properties, but doses at therapeutic levels have unacceptable side effects. Here we investigate folic acid modified D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-FA) as a potential carrier for controlled delivery of the drug.

Methods: Synthesized TPGS-FA was characterized by FTIR, UV-visible and ¹H NMR spectroscopy, and TPGS loaded with NC was evaluated for its ability to induce Apoptosis in Huh7 cells by Annexin V/PI and MTT assays, and observed by laser scanning confocal microscopy and inverted phase contrast microscopy.

Results: TPGS-FA/NC complexes were prepared successfully, and were homogenious with a uniform size of ~ 14 nm diameter. NC was released from the TPGS-FA/NC complexes in a controlled and sustained manner under physiological conditions (pH 7.4). Furthermore, its cytotoxicity to hepatocarcinoma cells was greater than that of free NC.

Conclusions: TPGS-FA is shown to be useful carrier for drugs such as NC, and TPGS-FA/NC could potentially be a potent and safe drug for the treatment of hepatocellular carcinoma.