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HDL nanoparticles have wound healing and anti-inflammatory properties and can topically deliver miRNAs.

ABSTRACT: microRNAs regulate numerous biological processes, making them potential therapeutic agents. Problems with delivery and stability of these molecules have limited their usefulness as treatments. We demonstrate that synthetic high-density lipoprotein nanoparticles (HDL NPs) topically applied to the intact ocular surface are taken up by epithelial and stromal cells. microRNAs complexed to HDL NPs (miR-HDL NPs) are similarly taken up by cells and tissues and retain biological activity. Topical treatment of diabetic mice with either HDL NPs or miR-HDL NPs significantly improved corneal re-epithelialization following wounding compared with controls. Mouse corneas with alkali burn-induced inflammation, topically treated with HDL NPs, displayed clinical, morphological and immunological improvement. These results should yield a novel HDL NP-based eye drop for patients with compromised wound healing ability (diabetics) and/or corneal inflammatory diseases (e.g. dry eye).

SUBMITTER: Wang J

PROVIDER: S-EPMC7941746 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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HDL nanoparticles have wound healing and anti-inflammatory properties and can topically deliver miRNAs.

Wang Junyi J Calvert Andrea E AE Kaplan Nihal N McMahon Kaylin M KM Yang Wending W Lu Kurt Q KQ Peng Han H Thaxton C Shad CS Lavker Robert M RM

Advanced therapeutics 20200930 12

microRNAs regulate numerous biological processes, making them potential therapeutic agents. Problems with delivery and stability of these molecules have limited their usefulness as treatments. We demonstrate that synthetic high-density lipoprotein nanoparticles (HDL NPs) topically applied to the intact ocular surface are taken up by epithelial and stromal cells. microRNAs complexed to HDL NPs (miR-HDL NPs) are similarly taken up by cells and tissues and retain biological activity. Topical treatm ...[more]

PMID: 33709017

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Project description:BackgroundWound healing (WH) is a complex process involving several stages, such as hemostasis, inflammation, re-epithelialization, and remodeling. Many factors can impair WH, and different pharmacological approaches were studied to date, but the increase in antibiotic resistance, invasiveness, treatment duration, and high cost, have often hampered the resolution of the wound. In this study, we investigated the possible application of water-soluble carvacrol prodrugs (WSCPs) and hyaluronic acid (HA) and their formulations (WSCPs/HA) to improve WH and regulate the inflammatory response.Materials and methodsFirstly, the cytotoxicity of 0.1, 1 and 10 µg/mL of HA, WSCPs and WSCPs/HA formulations were evaluated on HaCaT cells and THP-1 cell lines. The ability of WSCPs/HA formulations to modulate wound repair was evaluated in an in vitro model of WH, using HaCaT cells at 6, 18, and 24 h. The expression of WH mediators, after wound closure was determined by qRT-PCR. Following, we polarized THP-1 cells in M1/M2-like macrophages and tested the anti-inflammatory properties of WSCPs/HA formulations. After, we tested the in vitro WH model for the effects of conditioned medium (CM) from M1/M2-like cells cultured in the presence of WSCPs/HA.ResultsResults showed that WSCPs/HA formulations were able to significantly raise the wound closure rate, compared to the single constituents, promoting a complete wound closure after 18 h for WSCP1/HA (10 µg/mL) and after 24 h for WSCP2/HA (10 µg/mL), modulating the MMPs, TGFβ, and COX-2 gene expression. The effects of CM derived from M1/M2 polarized cells cultured in the presence of WSCPs/HA determined WH regulation, with a better ability of the WSCP2/HA formulation to modulate the time-dependent expression of reparative and inflammatory mediators.ConclusionOur data underline the possible application of WSCPs/HA formulations as bioactive agents for the regulation of the wound repair process by the modulation of inflammatory and remodeling phases, affecting the activity of immune cells.

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HDL nanoparticles have wound healing and anti-inflammatory properties and can topically deliver miRNAs.

Publications

HDL nanoparticles have wound healing and anti-inflammatory properties and can topically deliver miRNAs.

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