International Journal of Nanomedicine (Dec 2024)
Antimicrobial Effects of Thonningianin a (TA)-Loaded Chitosan Nanoparticles Encapsulated by a PF-127 hydrogel in Diabetic Wound Healing
Abstract
Qian Lin,1,* Fucheng Zhu,1,* Aji Shiye,1,* Runyu Liu,1,2 Xiaolan Wang,1 Zi Ye,1 Yinhuan Ding,3 Xiaolei Sun,1,4– 8 Yarong Ma9 1Department of General Surgery (Vascular Surgery), the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Hepatobiliary Pancreatic Vascular Surgery, the Second Affiliated Hospital of Chengdu Medical College, Chengdu, 610057, People’s Republic of China; 3Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, Sichuan, 646000, People’s Republic of China; 4Department of Interventional Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 5Laboratory of Nucleic Acids in Medicine for National High-Level Talent, Nucleic Acid Medicine of Luzhou Key Laboratory, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 6Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 7Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, 646000, People’s Republic of China; 8School of Cardiovascular Medicine and Sciences, King’s College London British Heart Foundation Centre of Research Excellence, Faculty of Life Science and Medicine, King’s College London, London, SE5 9NU, UK; 9Department of Ophthalmology, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaolei Sun; Yarong Ma, Email [email protected]; [email protected]; [email protected] and Purpose: Diabetic wounds are serious chronic complications of diabetes and can lead to amputation and death. Although considerable progress has been made in drugs and materials for treating it, it’s still an urgent clinical problem as the materials and drugs have potential therapeutic drawbacks, such as low delivery efficiency and poor tissue permeability. To promote diabetic wound healing, a composite of thonningianin A (TA)-loaded chitosan nanoparticles (CNPS) encapsulated by a Pluronic F-127 (PF-127) hydrogel (TA-CNPS-PF) was developed in this study.Methods: TA-CNPS was prepared by ionic gelation method and TA-CNPS was thoroughly dispersed into PF-127 hydrogel to prepare TA-CNPS-PF. The particle size, hydrogel structure, encapsulation ratio, release ratio, antimicrobial properties of TA-CNPS-PF were determined and the effect of TA-CNPS-PF on diabetic wounds was assessed. The effect of TA on macrophage polarization was also examined in vitro.Results: The particle size was approximately 100 nm of TA-CNPS-PF and the hydrogel had a homogeneous three-dimensional reticulation structure. The encapsulation efficiency of TA in the CNPS were 99.3% and the release ratio of TA-CNPS-PF was approximately 86% and has antimicrobial properties. TA-CNPS-PF promoted diabetic wound healing significantly. Histopathology confirmed that TA-CNPS-PF promoted complete re-epithelialization and adequate collagen deposition. TA promoted the polarization of M1 macrophages into M2 macrophages via light microscopy, immunocytometry and flow cytometry. TA-CNPS-PF also promoted an increase in the number of M2 macrophages in diabetic wounds.Conclusion: TA promotes diabetic wound healing by promoting the polarization of M1 macrophages into M2 macrophages and TA-CNPS-PF has good antimicrobial activity and a good drug release ratio in this study, which provides a new direction for the treatment of diabetic wounds and is expected to be highly advantageous in clinical diabetes wound therapy. Keywords: thonningianin A. TA, TA nanoparticle hydrogel, TA-CNPS-PF, diabetic wound, M1 macrophages, M2 macrophages