Secondary Structure Effect of Polypeptide on Reverse Thermal Gelation and Degradation of l/dl-Poly(alanine)–Poloxamer–l/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.

Injectable Biodegradable Hydrogels

“…Recently, poly(alanine)-poloxamerpoly(alanine) (PA-PLX-PA) was synthesized as a thermosensitive hydrogel. [62] Aqueous solutions of PA-PLX-PA underwent a sol-to-gel transition as the temperature increased. The sol-to-gel transition temperature was influenced by the molecular weight of each block and by the composition of PA. Based on FT-IR, DLS, 13 C NMR, circular dichroism (CD), transmission electron microscopy (TEM), and fluorescence spectroscopy studies, the PA transition from random coil to b-sheet and the decrease in molecular motion of PLX resulted in gelation.…”

Hybrid Block Copolymers Constituted by Peptides and Synthetic Polymers: An Overview of Synthetic Approaches, Supramolecular Behavior and Potential Applications

“…One of these examples was the study conducted on reverse thermal gelation of poly(alanine) end-capped poly(propylene glycol)-poly(ethylene glycol)-poly(propylene glycol) copolymers (PA-PLX-PA) [81]. The structure-property relationship of the sol-gel transition was investigated by varying PA and PLX lengths and L-Ala/DL-Ala ratio.…”

Multi-responsive hydrogels derived from the self-assembly of tethered allyl-functionalized racemic oligopeptides

“…Commonly used stimuli for responsive hydrogels include temperature 5, 6 , light, 7 pH, 8 enzymes, 9 sonication, 10 and oxidation-reduction. 11 Temperature, pH, and enzymes are particularly interesting stimuli for applications in biological systems.…”

“…Applied stimuli typically trigger construction or deconstruction of the hydrogel networks by either covalent 12 or non-covalent interactions. 5 Recently, hydrogels composed of materials with non-covalent interactions have received attention due to their ability to rapidly respond to physical or chemical stimuli, the versatility to self assemble into different nano- or micro-structures in different environments, and the ability to exhibit changes in macroscopic characteristics, such as sol-gel transitions. 13, 14 Compared with single stimulus-responsive systems, dual- or multi-responsive hydrogels provide higher flexibility in material fabrication and opportunities to achieve greater control of physical configurations or additional kinetic properties ( e.g .…”