Dissolving microneedles patch loaded with acanthopanax senticosus-derived extracellular vesicles to promote diabetic wounds healing

• 1、School of biomedical and pharmaceutical sciences, Guangdong University of Technology, Guangzhou 510006
• 2、College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming 650500

Abstract：Diabetic foot ulcers are one of the most common extensions of diabetes. The persistent inflammation and hypoxic environment present in diabetic ulcer wounds can lead to the presence of high expression of inflammatory factors, impaired micro angiogenesis and bacterial infection. Traditional methods are often ineffective in treatment due to their relatively single function. Here, extracellular vesicles (AS-EVs) of Siberian cherry origin were obtained from the traditional Chinese medicine Siberian cherry, and were co-loaded with polyethyleneimine (PEI 600) into soluble microneedles based on carboxymethyl chitosan (CMCS) and chondroitin sulphate (CS), to obtain microneedles AS-EVs/PEI 600 MN co-loaded with AS-EVs and PEI 600 (AP@MN) for promoting diabetic ulcer wound healing. Carboxymethyl chitosan and chondroitin sulfate were used as the substrates with good biosafety and degradability, and the microneedles were able to deliver the drugs precisely at the wound site. AS-EVs had the effects of scavenging reactive oxygen species (ROS), decreasing pro-inflammatory factors expression, and promoting angiogenesis, whereas PEI 600 was able to bind to and scavenge cfDNA in the wounds, and inhibit the growth of Escherichia coli (E.coli), Staphylococcus aureus (S.aureus), and MRSA. Therefore, AP@MN can achieve multiple functions, such as precise drug delivery, inflammation reduction, angiogenesis promotion, cfDNA removal, and bacterial growth inhibition, which shows great potential in the treatment of diabetic infected wounds.

Keywords： Pharmaceutical chemical industry Plant-derived extracellular vesicles Diabetic wounds Microneedling Polyethyleneimine?????