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Co-Delivery of Simvastatin and Microrna-21 Through Liposome Could Accelerates the Wound Healing Process Publisher Pubmed



Kiani M1 ; Moraffah F1 ; Khonsari F1 ; Kharazian B2 ; Dinarvand R2, 3 ; Shokrgozar MA4 ; Atyabi F1, 2
Authors

Source: Biomaterials Advances Published:2023


Abstract

The gene delivery approach, mainly microRNAs (miRNA) as key wound healing mediators, has recently received extensive attention. MicroRNA-21 (miR-21) has strongly impacted wound healing by affecting the inflammation and proliferation phases. Previous studies have also demonstrated the beneficial effect of simvastatin on wound healing. Therefore, we designed a dual-drug/gene delivery system using PEGylated liposomes that could simultaneously attain the co-encapsulation and co-delivery of miRNA and simvastatin (SIM) to explore the combined effect of this dual-drug delivery system on wound healing. The PEG-liposomes for simvastatin and miR-21 plasmid (miR-21-P/SIM/Liposomes) were prepared using the thin-film hydration method. The liposomes showed 85 % entrapment efficiency for SIM in the lipid bilayer and high physical entrapment of miR-21-P in the inner cavity. In vitro studies demonstrated no cytotoxicity for the carrier on normal human dermal fibroblast cells (NHDF) and 97 % cellular uptake over 2 h incubation. The scratch test revealed excellent cell proliferation and migration after treatment with miR-21-P/SIM/Liposomes. For the in vivo experiments, a full-thickness cutaneous wound model was used. The wound closure on day 8 was higher for Liposomal formulation containing miR-21-P promoting faster re-epithelialization. On day 12, all treated groups showed complete wound closure. However, following histological analysis, the miR-21-P/SIM/Liposomes revealed the best tissue regeneration, similar to normal functional skin, by reduced inflammation and increased re-epithelialization, collagen deposition and angiogenesis. In conclusion, the designed miR-21-P/SIM/Liposomes could significantly accelerate the process of wound healing, which provides a new strategy for the management of chronic wounds. © 2023
1. Current Advances in Wound Healing and Regenerative Medicine, Current Stem Cell Research and Therapy (2024)
2. Localized Delivery of Healing Stimulator Medicines for Enhanced Wound Treatment, Journal of Drug Delivery Science and Technology (2024)
3. Mesenchymal Stem Cells-Derived Exosomes for Wound Regeneration, Advances in Experimental Medicine and Biology (2018)
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