Hydrogel microneedle patch for treatment of liver fibrosis

Rationale: Chronic liver fibrosis is a common and irreversible disease in clinical practice, and Pirfenidone (PFD) has been shown to effectively inhibit the progression of liver fibrosis in multiple studies. However, some critically ill patients cannot take oral medications, and high dose and frequency of administration can cause higher physical burden to the critically ill. Therefore, we are committed to finding a material that can provide an efficient mode of drug delivery to address chronic disease.Methods: We have developed a hydrogel microneedle patch (MNP) based on GelMA material to provide sustained release of PFD for reducing dosing frequency, alleviating the physical burden, and enhancing therapeutic efficacy. In vitro experiments were conducted to verify the effectiveness of the microneedle patch, and a chronic liver fibrosis model was established in C57 mouse for further validation.Results: Gel-PFD MNP demonstrated good biocompatibility in vitro and in vivo studies. Cy7 fluorescence showed complete degradation of the MNP after 1 week in vivo. In vitro, Gel-PFD MNP inhibited fibroblast migration and proliferation. In mice treated with Gel-PFD, markers of fibrosis, inflammation and apoptosis in tissue or serum RNA and protein expression were relatively low, and liver enzymes and behavioral levels were also relatively normal.Conclusions: Gel-PFD has good biocompatibility and sustained-release abilities, which can significantly reduce the frequency of administration and has better anti-fibrosis ability than oral PFD. It has extremely positive implications for improving chronic liver injury in patients who are unable to eat or severely ill.