Reversible exposure of hydrophobic residues on albumin as a novel strategy for the formulation of nanodelivery vehicles of taxanes.

GARRO, A.G.; BELTRAMO D.M.; R.V. ALASINO; V. LEONHARD; HEREDIA V.; BIANCO I.D.

DOVE MEDICAL PRESS LTD

Lugar: Auckland; Año: 2011 vol. 6 p. 1193 - 1193

e report herein a novel strategy for the preparation of protein based nanodelivery vehicles of hydrophobic active pharmaceutical ingredients (APIs). The procedure consists of three steps: a) the exposure of hydrophobic residues of a protein to a pH-induced partial unfolding; b) the interaction between hydrophobic residues on the protein and the hydrophobic API, and c) a final step where the structure of the protein is reversed to a native-like state by returning to neutral pH. As a proof of concept, the interaction of paclitaxel (Ptx) with partially unfolded states of human serum albumin (HSA) was evaluated as a potential method to prepare water soluble complexes of the taxane with albumin. We found that Ptx readily binds to pH-induced partially unfolded albumin leading to the formation of optically clear water soluble complexes. The complexes thus formed were more stable in solution when the albumin native state was, at least partially, restored by neutralization of the solution to a