Temperature and pH sensitive hydrogels based on N-acryloyl-L-histidine and N-acryloyl-L-phenylalanine

Purpose: To study new materials exhibiting reversible sensitivity to environmental conditions in view of their potential application in drug delivery technology. Methods: The monomers N-acryloyl-L-histidine (Hist) and N-acryloyl-L-phenylalanine (Phe) were obtained by the acylation reaction of acryloyl chloride with the corresponding a-aminoacid in alkaline solution. Homopolymers and copolymers with N-isopropylacrylamide were obtained by radical polymerization in both soluble and cross-linked forms. All compounds were characterized by viscometry (h/C), potentiometry (basicity constants, logK) and solution calorimetry (enthalpy -DH° and entropy DS° changes). The equilibrium degree of swelling (EDS) for hydrogels was monitored at different temperature and pHs in buffers at the ionic strength of 0.15M NaCl. Results: Thermodynamic data for the protonation of basic groups in polymers were similar for soluble and cross-linked closer-structured compounds. The EDS in relation to pH for cross-linked poly(Hist) showed the peculiar ampholyte character to be very similar to that showed by the soluble analogue, when the reduced viscosity (h/C) was considered. A linear relationship of EDS in relation to h/C was found. The EDS for cross-linked copolymers of poly(Phe) was strongly dependent on temperature and pH, showing greater EDS at higher pH than its logK, even at higher temperatures. Conclusions: Both soluble and cross-linked polymers were not toxic against RAW 264 cell lines. This suggests the opportunity to use anionic or ampholyte polymers in the formulation of drug delivery products.