Wound healing and antibacterial chitosan-genipin hydrogels with controlled drug delivery for synergistic anti-inflammatory activity

• Published in: International journal of biological macromolecules Vol. 203; pp. 679 - 694
• Main Authors: Andrade del Olmo, Jon, Pérez-Álvarez, Leyre, Sáez-Martínez, Virginia, Benito-Cid, Sandra, Ruiz-Rubio, Leire, Pérez-González, Raúl, Vilas-Vilela, José Luis, Alonso, José María
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2022
• Subjects: Anti-Bacterial Agents - pharmacology; Anti-Inflammatory Agents - pharmacology; Antibacterial; Biocompatibility; Chitosan - pharmacology; Chitosan hydrogels; Drug delivery; Hydrogels - pharmacology; Iridoids; Synergistic anti-inflammatory activity; Wound Healing; Biocompatibility; Drug delivery; Wound healing; Antibacterial; Chitosan hydrogels; Synergistic anti-inflammatory activity
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2022.01.193

Chitosan (CHI) based hydrogels promote wound healing and relieve inflammations and chronic infections. However, in hardly healable ulcers with excessively painful inflammations, anti-inflammatory activity of hydrogels can be enhanced by the sustained release of non-steroidal anti-inflammatory drugs or combining them with antibiotics. Thus, CHI was crosslinked with genipin (GP) to obtain biocompatible hydrogels. Moreover, their antibacterial activity was confirmed against Staphylococcus aureus and Escherichia coli with an almost 100% bacteria reduction and a potential antibacterial efficacy (R > 2). Furthermore, hydrogels effective healing of ulcerated wounds was corroborated by a significant improvement in metabolic activity (95.58 ± 4.40%), collagen and elastin quantities (1.48 ± 0.07 μg collagen and 5.82 ± 0.73 μg elastin per mg dermal tissue) and histological analysis. Finally, the sustained release of acetylsalicylic acid (ASA), cefuroxime (CFX), tetracycline (TCN) and amoxicillin (AMX) were studied, as well as their anti-inflammatory activity. Results confirm the synergistic anti-inflammatory activity by the significant reduction in the amount of pro-inflammatory cytokines when ASA was combined with CFX (5.39 ± 0.81 ng·mL−1 TNF-α), TCN (4.70 ± 0.21 ng·mL−1 TNF-α and 49.06 ± 9.64 ng·mL−1 IL-8), and AMX (2.28 ± 0.36 ng·mL−1 TNF-α, 14.84 ± 5.57 ng·mL−1 IL-8, and total IL-6 removal). [Display omitted] •CHI-GP hydrogel formulations were optimized to achieve long-term biocompatible biomaterials.•Antibacterial and wound healing (ulcerated skin) properties of hydrogels were proved.•Loading and sustained release of ASA, CFX, TCN and AMX from CHI-GP hydrogels was studied.•Hydrogels loaded with ASA-antibiotic combinations had a synergistic anti-inflammatory activity.