Reversible Thermoresponsive Peptide-PNIPAM Hydrogels for Controlled Drug Delivery

Mixed thermoreversible gels were successfully fabricated by the addition of a thermosensitive polymer, poly(N-isopropylacrylamide) (PNIPAM), to fibrillar nanostructures self-assembled from a short peptide I3K. When the temperature was increased above the lower critical solution temperature of the PNIPAM, the molecules collapsed to form condensed globular particles, which acted as cross-links to connect different peptide nanofibrils and freeze their movements, resulting in the formation of a hydrogel. Since these processes were physically driven, such hydrogels could be reversibly switched between the sol and gel states as a function of temperature. As a model peptide, I3K was formulated with PNIPAM to produce a thermoreversible sol-gel system with a transition temperature of similar to 33 degrees C, which is just below the body temperature. The antibacterial peptide of G(IIKK)(3)I-NH2 could be conveniently encapsulated in the hydrogel by the addition of the solution at lower temperatures in the sol phase and then increasing the temperature to be above 33 degrees C for gelation. The hydrogel gave a sustained and controlled linear release of G(IIKK)(3)I-NH2 over time. Using the peptide nanofibrils as three-dimensional scaffolds, such thermoresponsive hydrogels mimic the extracellular matrix and could potentially be used as injectable hydrogels for minimally invasive drug delivery or tissue engineering.