DELIVERY OF ANTI-MICRORNA-21 BY LUNG-TARGETED LIPOSOMES FOR PULMONARY FIBROSIS TREATMENT

Delivery of anti-microRNA-21 by lung-targeted liposomes for pulmonary fibrosis treatment

Delivery of anti-microRNA-21 by lung-targeted liposomes for pulmonary fibrosis treatment

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Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder with a low survival rate.Pulmonary fibrosis is one of the complications of COVID-19 and has a high prevalence in COVID-19 patients.Currently, no effective therapies other than lung transplantation are available to cure IPF and post-COVID-19 pulmonary fibrosis.MicroRNAs are small non-coding RNAs that mediate the development and progression of pulmonary fibrosis, thus making them potent drug candidates for this serious disease.MicroRNA-21 (miR-21) promotes not only the differentiation of fibroblasts to myofibroblasts but also epithelial-mesenchymal transition, both of Wither Straps which have been proposed as fundamental processes in pulmonary fibrosis development.

Delivery of anti-miR-21 to block the miR-21-associated fibrogenic pathways represents a promising therapy for pulmonary fibrosis.However, microRNA treatment is challenged by quick degradation of RNA in blood, poor cellular uptake, and off-target effects.To overcome these challenges, we developed a lung-targeted, cationic liposome formulation to encapsulate anti-miR-21, enhance its delivery efficiency, and improve the therapeutic efficacy.We optimized the liposome formulation and demonstrated the anti-fibrotic effects using both in vitro and in vivo lung fibrosis models.Our results showed that anti-miR-21 delivered by cationic liposomes suppressed myofibroblast Cables differentiation, reduced the synthesis of extracellular matrix, and inhibited fibrosis progression.

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