Hydrophilic and hydrophobic amino acid copolymers for nano-comminution of poorly soluble drugs

Nano-comminution has successfully brought nanoparticle formulations of poorly soluble drugs to our daily life. The key for the successful nano-comminution of a drug is the choice of a proper polymeric steric stabilizer. To systematically elucidate the rationale of stabilizer selection, two types of helical amino acid copolymers, relatively hydrophilic and hydrophobic copolymers, were used in nano-comminution. The hydrophilic copolymers had lysine as their major component. The addition of relatively hydrophobic leucine and phenylalanine to them could not make significant changes in particle size. However, when a small amount of hydrophilic glutamic acid or lysine was added into elastin-like hydrophobic copolymers of valine, glycine, and proline, significant composition dependence was found. Therefore, specific interactions between the functional groups of polymers and drug surfaces seem to be important for successful nano-comminution. The stimuli responsive behavior of the hydrophobic copolymer induced the temperature dependence of particle size. (C) 2009 Elsevier B.V. All rights reserved.