Thermo-responsive copolymers for enzyme-triggered drug delivery and bioresorbable scaffolds

Statement of Purpose: N-isopropylacrylamide (NIPAAm) copolymers have a lower critical solution temperature (LCST) due to their amphiphilic nature, which allows them to be injectable below LCST and to solidify in situ above the LCST. [1] The aim of this study was to investigate amino acid substitution in an enzyme degradable side group of a NIPAAm copolymer for drug delivery and bioresorbable scaffolds for tissue engineering. Therefore, in this work, a series of NIPAAm-based copolymers with hydrophobic side groups containing the Ala-Pro-Gly-Leu collagenase substrate peptide sequence were synthesized as in situ forming, injectable copolymers. Collagenase is a matrix metalloproteinase (MMP) that plays an important role enabling cell migration and tissue remodelling. [2] The Gly-Leu peptide bond in these polypeptides is cleaved by collagenase, converting the side group into the more hydrophilic GAPG-COOH, thus increasing the LCST of the hydrogel. [1] The side groups Gly-Ala-Pro-Gly-Leu-Phe-NH2 (GAPGLF-NH2), Gly-Ala-Pro-Gly-Leu-Leu-NH2 (GAPGLL-NH2), and Gly-Ala-Pro-Gly-Leu-Val-NH2 (GAPGLV-NH2) were used to synthesize poly(NIPAAm-co-peptide) copolymers.