Bioresponsive Copolymers of Poly(N-isopropylacrylamide) with Enzyme-Dependent Lower Critical Solution Temperatures

• Published in: Biomacromolecules Vol. 11; no. 5; pp. 1154 - 1159
• Main Authors: Overstreet, Derek J, Dhruv, Harshil D, Vernon, Brent L
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 10.05.2010
• Subjects: Acrylamides - chemistry; Acrylic Resins; Applied sciences; Calorimetry, Differential Scanning; Chromatography, Gel; Exact sciences and technology; Magnetic Resonance Spectroscopy; Organic polymers; Physicochemistry of polymers; Polymers - chemistry; Polymers with particular properties; Preparation, kinetics, thermodynamics, mechanism and catalysts; Solutions; Temperature; Biological properties; Peptides; Enzyme; Biodegradability; Metalloendopeptidases; Acrylamide derivative copolymer; Experimental study; Amidation; Lateral group; Peptidases; Cloud point; Chemical modification; Preparation; Enzymatic digestion; Hydrolases; Acrylate copolymer; Aqueous solution; Radical copolymerization; Interstitial collagenase
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm100035f

Novel thermoreversible copolymers of N-isopropylacrylamide (NIPAAm) with collagenase-sensitive solubility behavior were synthesized by radical polymerization of poly(NIPAAm-co-NASI) and nucleophilic substitution of custom peptides GAPGL-NH2 and GAPGLF-NH2. The materials were characterized by nuclear magnetic resonance spectroscopy (NMR), gel permeation chromatography in conjunction with static light scattering, differential scanning calorimetry (DSC), and cloud point determination. Successful synthesis and specific degradation by collagenase above and below the material LCST was confirmed by NMR. The LCST behavior of the polymers was affected by collagenase. The LCST of the copolymers, as measured by cloud point determination, increased by 1 and 9 °C, respectively, after enzymatic degradation. DSC thermographs indicated increased polymer solubility after enzymatic degradation because of a reduced energy of gelation. These results demonstrate the significant impact of a single amino acid on the LCST behavior of thermosensitive copolymers. Furthermore, the results suggest that comonomers in similar systems could be designed to elicit phase transitions or conformation changes in response to a variety of enzymes for which the substrate structure is known.