Dual stimuli-responsive polyurethane-based hydrogels as smart drug delivery carriers for the advanced treatment of chronic skin wounds

Abstract

The design of multi-stimuli-responsive vehicles for the controlled and localized release of drugs is a challenging issue increasingly catching the attention of many research groups working on the advanced treatment of hard-to-close wounds. In this work, a thermo- and pH-responsive hydrogel (P-CHP407) was prepared from an ad hoc synthesized amphiphilic poly(ether urethane) (CHP407) exposing a significant amount of –COOH groups (8.8 ± 0.9 nmol/g polymer ). The exposure of acid moieties in P-CHP407 hydrogel led to slightly lower initial gelation temperature (12.1 °C vs. 14.6 °C, respectively) and gelation rate than CHP407 hydrogel, as rheologically assessed. Nanoscale hydrogel characterization by Low Field NMR (LF-NMR) spectroscopy suggested that the presence of carboxylic groups in P-CHP407 caused the formation of bigger micelles with a thicker hydrated shell than CHP407 hydrogels, as further proved by Dynamic Light Scattering analyses. In addition, P-CHP407 hydrogel showed improved capability to change its internal pH compared to CHP407 one when incubated with an alkaline buffer (pH 8) (e.g., pH change_5min = 3.76 and 1.32, respectively). Moreover, LF-NMR characterization suggested a stronger alkaline-pH-induced interaction of water molecules with micelles exposing –COOH groups. Lastly, the hydrogels were found biocompatible according to ISO 10993 and able to load and release Ibuprofen: delivery kinetics of Ibuprofen was enhanced by P-CHP407 hydrogels at alkaline pH, suggesting their potential use as smart delivery systems in the treatment of chronic infected wounds.

Role of Polymer Concentration and Crosslinking Density on Release Rates of Small Molecule Drugs

“…Currently, the majority of the studies focus on the stimulus responsiveness of hydrogels to develop a wide variety of smart systems that exhibit tailorable drug delivery properties in response to one or more (dual-responsive) stimuli, such as pH, temperature, light, enzymes, etc. [16][17][18][19]. Fewer studies focus on manipulating and studying the role of inherent hydrogel properties (i.e., monomer concentration, crosslinking density) to tailor drug delivery amounts and rates [20][21][22][23][24][25][26].…”

Glucose and MMP-9 dual-responsive hydrogel with temperature sensitive self-adaptive shape and controlled drug release accelerates diabetic wound healing

“…Hydrogels are reasonable wound dressings that create a moist environment for wounds, absorb tissue exudates, and transport functional drugs to accelerate wound healing. In recent years, stimuli-responsive drug-loaded hydrogels have attracted much attention in biomedicine, as they respond to the external environment—such as reactive oxygen species (ROS) [ 20 , 21 ], temperature [ 22 ], pH [ 23 , 24 ], glucose [ 23 ], enzymes [ 8 , 9 ]—and provide "smart" control for the release of drugs. High concentration of glucose and MMP-9 are important factors hindering chronic diabetic wound healing [ 6 , 14 ], and the double-stimulus responsive drug-loaded hydrogel targeting glucose and MMP-9 is a promising dressing.…”

Electrospun Core–Sheath Nanofibers with Variable Shell Thickness for Modifying Curcumin Release to Achieve a Better Antibacterial Performance

“…The original hydrophobic property of water-insoluble drugs remarkably limits their treatment efficiency [ 5 ]. Fortunately, diverse drug delivery systems have been intensively studied to address the issue of drugs with poor bioavailability, such as lipid nanoparticles [ 6 , 7 ], nanoemulgel [ 8 , 9 ], electrospun fibers [ 10 ], 3D printing [ 11 ], and hydrogel [ 12 , 13 , 14 ]. The water solubility and stability of drugs can be enhanced through controlled release or targeted drug delivery, thus promoting the absorption of drugs.…”