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

Rossella Laurano; Monica Boffito; Michela Abrami; Mario Grassi; Alice Zoso; Valeria Chiono; Gianluca Ciardelli

doi:10.1016/j.bioactmat.2021.01.003

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

Bioact Mater. 2021 Feb 19;6(9):3013-3024. doi: 10.1016/j.bioactmat.2021.01.003. eCollection 2021 Sep.

Authors

Rossella Laurano¹, Monica Boffito¹, Michela Abrami², Mario Grassi², Alice Zoso¹, Valeria Chiono¹, Gianluca Ciardelli¹

Affiliations

¹ Politecnico di Torino, Mechanical and Aerospace Engineering Department, Corso Duca degli Abruzzi 24, 10129, Torino, Italy.
² Università degli Studi di Trieste, Department of Engineering and Architecture, Via Alfonso Valerio 6/1, 34127, Trieste, Italy.

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.

Keywords: Advanced wound treatment; Drug delivery system; LF-NMR characterization; Polyurethane hydrogel; Stimuli-responsive hydrogel; pH-triggered release.