Reverse thermal gelation of PAF-PLX-PAF block copolymer aqueous solution.

The aqueous solution of poly(L-Ala-co-L-Phe)-poly(propylene glycol)-poly(ethylene glycol)-poly(propylene glycol)-poly(L-Ala-co-L-Phe) block copolymers (PAF-PLX-PAF) in a concentration range of 6.0-10.0 wt % underwent sol-to-gel transition as the temperature increased from 10 to 50 degrees C. Circular dichroism spectra, hydrophobic dye solubilization, dynamic light scattering, and transmission electron microscopy image of the polymer suggest that the polymers form micelles in water, where the hydrophilic (PLX) blocks form a shell and the hydrophobic (PAF) blocks form a core of the micelle. Circular dichroism, FTIR, and (13)C NMR spectra suggest that sol-to-gel transition accompanies partial strengthening of the beta-sheet structure of PAF and a decrease in molecular motion of the PLX. The sol-to-gel transition temperature could be controlled by varying the molecular weight of PAF and PLX blocks, the ratio of Ala to Phe, and the corresponding secondary structure of the polypeptide.

Enzymatically degradable temperature-sensitive polypeptide as a new in-situ gelling biomaterial.

We are reporting a poly (ethylene glycol)-block-poly(alanine-co-phenyl alanine) (PEG-PAF) aqueous solution that undergoes sol-to-gel transition as the temperature increases. The sol-to-gel transition was observed at as low a concentration as 3.0-7.0 wt.%. Micellar aggregation accompanying small conformational changes of the peptide from random coils to beta-sheets is suggested as the sol-to-gel transition mechanism of the PEG-PAF aqueous solution. The PEG-PAF is stable in phosphate buffered saline, however, it degraded in the subcutaneous layer of rats. In vitro study showed that proteolytic enzymes such as cathepsin B, cathepsin C, and elastase that are present in the subcutaneous layer of the mammalian tissue might be responsible for the degradation of the polymer in rats. As a feasibility study of this material, a single shot of an aqueous insulin formulation (13.8 mg insulin/kg) showed a hypoglycemic effect over 18 days in rats. The current functional polypeptide may be very promising as an in-situ gelling system for tissue engineering, cell/stem cell therapy, and drug delivery.