Secondary structure effect of polypeptide on reverse thermal gelation and degradation of L/DL-poly(alanine)-poloxamerL/DL-poly(alanine) copolymers

Abstract

Poly(alanine) end-capped poly(propylene glycol)-poly(ethylene glycol)-poly(propylene glycol) (PA-PLX-PA) aqueous solutions underwent sol-to-gel transition as the temperature increased. On the basis of FTIR spectra, circular dichroism spectra, 13C NMR spectra, transmission electron microscopic images, fluorescence spectra, and dynamic light scattering studies, increases in the β-sheet conformation of the polyalanine (PA) and dehydration of the poly(propylene glycol)-poly(ethylene glycol)-poly(propylene glycol) (PLX) were suggested as the sol-to-gel transition mechanism. The sol-to-gel transition temperature could be controlled by molecular parameters of the PA-PLX-PA such as molecular weight of PA, molecular weights of PLX, and L-Ala/DL-Ala ratio. The PA-PLX-PA was significantly degraded in the subcutaneous layer of rats over 15 days; however, it was stable in phosphate buffer saline over the same period of time. Poly(propylene glycol)/poly(ethylene glycol) block copolymers suffer from short gel duration for biomedical applications, whereas the current polypeptide-based polymer is unique in that it shows prolonged (> 15 days) gel duration and the sol-to-gel transition involves the secondary structural change of the polypeptide. © 2008 American Chemical Society.