Reversible Thermoresponsive Peptide-PNIPAM Hydrogels for Controlled Drug Delivery.

Mixed thermoreversible gels were successfully fabricated by the addition of a thermosensitive polymer, poly(-isopropylacrylamide) (PNIPAM), to fibrillar nanostructures self-assembled from a short peptide IK. 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, IK was formulated with PNIPAM to produce a thermoreversible sol-gel system with a transition temperature of ∼33 °C, which is just below the body temperature. The antibacterial peptide of G(IIKK)I-NH 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 °C for gelation. The hydrogel gave a sustained and controlled linear release of G(IIKK)I-NH 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.