Reversible Thermoresponsive Peptide–PNIPAM Hydrogels for Controlled Drug Delivery

Abstract

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.

Poly(N-isopropylacrylamide)-Based Thermoresponsive Composite Hydrogels for Biomedical Applications

“…Pure PNIPAM hydrogels usually have a limited drug loading ability and can hardly realize a sustained release of drugs due to simple physical interaction forces in the hydrogels, which greatly hinder their applications in drug delivery. Our group has fabricated a hybrid hydrogel by mixing a short peptide of I 3 K with PNIPAM ( Figure 2A) [92]. In this system, I 3 K self-assembled fibrils entangle with PNIPAM to form a 3D hydrogel network upon temperature increase to above 33 • C. This sol-gel process is reversible with temperature change because it is driven by physical interactions including hydrogen bonding, hydrophobic interaction and steric hindrance ( Figure 2B) [92,93].…”

Nanogel: A Versatile Nano-Delivery System for Biomedical Applications

“…Moreover, the LCST of pNIPAm can be regulated by chain modifications. Hence, pNIPAm-based copolymers with thermosensitive properties were synthesized by chemical crosslinking with other monomers to form various DDSs, including nanogel [33,34], and hydrogel [35][36][37]. In the recent report, by initiating the polymerization of NIPAm with AA and N- [3-(dimethylamino) propyl] methacrylamide (DMAPMA), the volume phase transition temperature (VPTT) of pNIPAm-based nanogels was adjusted to near the physiological temperature (37 • C).…”

Research progress in the application of in situ hydrogel system in tumor treatment

“…Temperature-sensitive in situ hydrogels are liquid or semisolid at room temperature. After administration, as the temperature rises from room temperature to body temperature, a phase transition occurs immediately at the site of application and the liquid or semi-solid form solidifies into hydrogel, resulting in good adhesion and slow release effects (Chu et al, 2013;Lin et al, 2014;Rarokar et al, 2016;Cao et al, 2019).…”