*Article* **Quercetin/Hydroxypropyl-**β**-Cyclodextrin Inclusion Complex-Loaded Hydrogels for Accelerated Wound Healing**

**Nutsarun Wangsawangrung <sup>1</sup> , Chasuda Choipang 1,2, Sonthaya Chaiarwut 1,2, Pongpol Ekabutr <sup>1</sup> , Orawan Suwantong 3,4, Piyachat Chuysinuan <sup>5</sup> , Supanna Techasakul <sup>5</sup> and Pitt Supaphol 1,2,\***


**Abstract:** This study concentrated on developing quercetin/cyclodextrin inclusion complex-loaded polyvinyl alcohol (PVA) hydrogel for enhanced stability and solubility. Quercetin was encapsulated in hydroxypropyl-β-cyclodextrin (HP-β-CD) by the solvent evaporation method. The prepared quercetin/HP-β-CD inclusion complex showed 90.50 ± 1.84% encapsulation efficiency (%EE) and 4.67 ± 0.13% loading capacity (%LC), and its successful encapsulation was confirmed by FT-IR and XRD. The quercetin/HP-β-CD inclusion complex was well dispersed in viscous solutions of PVA in various amounts (0.5, 1.0, 1.5. 2.5, and 5.0% *w/v* ratio), and the drug-loaded polymer solution was physically crosslinked by multiple freeze–thaw cycles to form the hydrogel. The cumulative amount of quercetin released from the prepared hydrogels increased with increasing concentrations of the inclusion complex. The introduction of the inclusion complex into the PVA hydrogels had no influence on their swelling ratio, but gelation and compressive strength reduced with increasing inclusion complex concentration. The potential cytotoxicity of quercetin/HP-β-CD inclusion complex hydrogels was evaluated by MTT assay and expressed as % cell viability. The results show biocompatibility toward NCTC 929 clone cells. The inhibitory efficacy was evaluated with 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay, and the results show a higher level of antioxidant activity for quercetin/HP-β-CD inclusion complex hydrogels compared with free quercetin. The findings of our study indicate that the developed quercetin/HP-β-CD inclusion complex hydrogels possess the required properties and can be proposed as a quercetin delivery system for wound-healing applications.

**Keywords:** quercetin; cyclodextrin; polyvinyl alcohol; inclusion complex; hydrogel
