Coumarin/β-Cyclodextrin Inclusion Complexes Promote Acceleration and Improvement of Wound Healing

• Published in: ACS applied materials & interfaces 2024-06, Vol.16 (24), p.30900-30914
• Main Authors: Dutra, Flávia Viana Avelar, Francisco, Carla Santana, Carneiro Pires, Bruna, Borges, Marcella Matos Cordeiro, Torres, Ana Luiza Horta, Resende, Vivian Alexandra, Mateus, Marcella Fernandes Mano, Cipriano, Daniel Fernandes, Miguez, Flávio Bastos, Freitas, Jair Carlos Checon de, Teixeira, Jéssika Poliana, Borges, Warley de Souza, Guimarães, Luciana, da Cunha, Elaine Fontes Ferreira, Ramalho, Teodorico de Castro, Nascimento, Clebio Soares, De Sousa, Frederico Barros, Costa, Raquel Alves, Lacerda, Valdemar, Borges, Keyller Bastos
• Format: Article
• Language: English
• Subjects: Animals; beta-Cyclodextrins - chemistry; Biological and Medical Applications of Materials and Interfaces; Coumarins - chemistry; Coumarins - pharmacology; Humans; Male; Mice; Solubility; Wound Healing - drug effects
• ISSN: 1944-8244; 1944-8252; 1944-8252
• DOI: 10.1021/acsami.4c05069

Coumarins have great pharmacotherapeutic potential, presenting several biological and pharmaceutical applications, like antibiotic, fungicidal, anti-inflammatory, anticancer, anti-HIV, and healing activities, among others. These molecules are practically insoluble in water, and for biological applications, it became necessary to complex them with cyclodextrins (CDs), which influence their bioavailability in the target organism. In this work, we studied two coumarins, and it was possible to conclude that there were structural differences between 4,7-dimethyl-2H-chromen-2-one (DMC) and 7-methoxy-4-methyl-2H-chromen-2-one (MMC)/β-CD that were solubilized in ethanol, frozen, and lyophilized (FL) and the mechanical mixtures (MM). In addition, the inclusion complex formation improved the solubility of DMC and MMC in an aqueous medium. According to the data, the inclusion complexes were formed and are more stable at a molar ratio of 2:1 coumarin/β-CD, and hydrogen bonds along with π–π stacking interactions are responsible for the better stability, especially for (MMC)2@β-CD. In vivo wound healing studies in mice showed faster re-epithelialization and the best deposition of collagen with the (DMC)2@β-CD (FL) and (MMC)2@β-CD (FL) inclusion complexes, demonstrating clearly that they have potential in wound repair. Therefore, (DMC)2@β-CD (FL) deserves great attention because it presented excellent results, reducing the granulation tissue and mast cell density and improving collagen remodeling. Finally, the protein binding studies suggested that the anti-inflammatory activities might exert their biological function through the inhibition of MEK, providing the possibility of development of new MEK inhibitors.