Improvements in the water dispersibility of paclitaxel by complexing with synthetic peptides derived from β-casein.

Recently, digestive peptides prepared as a casein hydrolysate have been found to be an effective dispersant for the poorly water-soluble drug paclitaxel (Ptx). A major hydrophobic peptide in the digested peptides was identified as YQEPVLGPVRGPFPIIV (PepY) by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry with the "LIFT" technique. In the present study, three peptides PepY, VVVPPFLQPEVMGVSKV (PepV), and KFQSEEQQQTEDELQDK (PepK) were chemically synthesized by Fmoc solid-phase synthesis to compare their function as dispersants for Ptx. PepV and PepK are the most hydrophobic and hydrophilic peptides, respectively, in the sequence of β-casein, which are the same length as PepY (PepY, PepV, and PepK are abbreviated as Peps). The complex between Ptx and Peps (Ptx-Peps) was prepared by mixing an ethanol solution of Ptx and an aqueous solution of Peps, followed by lyophilization. The complex with PepV, which is estimated to be the most hydrophobic of the peptides, had the greatest ability to improve the water dispersibility of Ptx. The water dispersibility of the complexes between Ptx and PepY and PepV increased as the amount of the peptides increased, whereas PepK was not effective in enhancing the dispersibility of Ptx. Furthermore, a peptide mixture obtained from a casein hydrolysate [Pep (fraction A)] was more effective for the enhancement of Ptx dispersibility than the single peptide PepY. These results suggests that a variety of peptides in the casein hydrolysate contribute toward complexation with Ptx.