Secondary Structure Effect of Polypeptide on Reverse Thermal Gelation and Degradation of L/DL-Poly(alanine)-Poloxamer-L/DL-Poly(alanine) Copolymers

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, C-13 NMR spectra, transmission electron microscopic images, fluorescence spectra, and dynamic light scattering studies, increases in the beta-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.