Reversible Thermoresponsive Peptide–PNIPAM Hydrogels for Controlled Drug Delivery

• Published in: Biomacromolecules Vol. 20; no. 9; pp. 3601 - 3610
• Main Authors: Cao, Meiwen, Wang, Yu, Hu, Xuzhi, Gong, Haoning, Li, Ruiheng, Cox, Henry, Zhang, Jing, Waigh, Thomas A, Xu, Hai, Lu, Jian Ren
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 09.09.2019
• Subjects: antimicrobial peptides; body temperature; crosslinking; drug delivery systems; drugs; encapsulation; extracellular matrix; freezing; gelation; hydrogels; nanofibers; polymers; thermosensitivity; tissue engineering
• ISSN: 1525-7797; 1526-4602; 1526-4602
• DOI: 10.1021/acs.biomac.9b01009

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 ∼33 °C, which is just below the body temperature. The antibacterial peptide of G­(IIKK)3I-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 °C for gelation. The hydrogel gave a sustained and controlled linear release of G­(IIKK)3I-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.