Reversible Thermoresponsive Peptide–PNIPAM Hydrogels for Controlled Drug\nDelivery

Abstract

Mixed\nthermoreversible gels were successfully fabricated by the\naddition of a thermosensitive polymer, poly­(<i>N</i>-isopropylacrylamide)\n(PNIPAM), to fibrillar nanostructures self-assembled from a short\npeptide I₃K. When the temperature was increased above the\nlower critical solution temperature of the PNIPAM, the molecules collapsed\nto form condensed globular particles, which acted as cross-links to\nconnect different peptide nanofibrils and freeze their movements,\nresulting in the formation of a hydrogel. Since these processes were\nphysically driven, such hydrogels could be reversibly switched between\nthe sol and gel states as a function of temperature. As a model peptide,\nI₃K was formulated with PNIPAM to produce a thermoreversible\nsol–gel system with a transition temperature of ∼33\n°C, which is just below the body temperature. The antibacterial\npeptide of G­(IIKK)₃I-NH₂ could be conveniently\nencapsulated in the hydrogel by the addition of the solution at lower\ntemperatures in the sol phase and then increasing the temperature\nto be above 33 °C for gelation. The hydrogel gave a sustained\nand controlled linear release of G­(IIKK)₃I-NH₂ over time. Using the peptide nanofibrils as three-dimensional scaffolds,\nsuch thermoresponsive hydrogels mimic the extracellular matrix and\ncould potentially be used as injectable hydrogels for minimally invasive\ndrug delivery or tissue engineering.