Controlled release of phosphorothioates by protein-based polymers.

Protein-based polymers are water soluble at lower temperatures but undergo a phase transition with increasing temperature. The polymers' hydrophobicity controls the transition temperature and the free energy of its charged groups through an apolar-polar repulsive free energy of hydration, which drives the binding of charged drugs. Binding and release of phosphorothioates were obtained with polymers containing 1 lysine alone or coupled with 2 to 5 phenylalanines per 30 residues. Release rates from 4 to 64 nmol/ cm2/day were maintained constant for 8 to 2 weeks/mm, respectively. We demonstrated the ability of protein-based polymers to deliver nucleic acid based therapeutics with high programmability.