Protein-based micelles for the delivery of hydrophobic active compounds

A method of producing an amphiphilic fusion protein that spontaneously self-assembles to form a stable micelle, the method comprising:

• (a) introducing into a host cell an expression vector comprising a chimeric nucleic acid construct comprising, in the 5′ to 3′ direction, a promoter suitable for directing expression in a host cell operably linked to a nucleic acid sequence encoding an amphiphilic fusion protein having Formula (I):
• S/I—X—H1—H2, wherein S— is a solubilizing moiety, I— is an insolubilizing moiety, —X— is a peptide sequence comprising a proteolytic or chemical cleavage site, —H1— is a hydrophilic peptide, and —H2 is a hydrophobic peptide;
• (b) growing the host cell under conditions that allow for expression of the chimeric nucleic acid to produce the amphiphilic fusion protein;
• (c) purifying the amphiphilic fusion protein;
• and
• (d) contacting the amphiphilic fusion protein with a protease or a reagent to induce chemical cleavage to provide an amphiphilic fusion protein having Formula (II):
• H1—H2.

A micelle comprising an amphiphilic fusion protein comprising:

• (i) a hydrophilic peptide (H1);
• and
• (ii) a hydrophobic peptide (H2);
• wherein the H1 comprises an intrinsically disordered peptide (IDP) sequence selected from the group consisting of one or more polypeptide sequences from a human neurofilament protein, a San1 protein, an Hsp-33 protein, an E1A protein, a PhD protein, a Sic1 protein, a WASP protein, a p27 protein, a CREB protein, a PUP protein, and a LEA protein.