Bioinspired Prolactin Pulse Release from Responsive Microneedles for Inhibiting Fatty Liver Formation.

Abstract

Hormonal mechanisms of fatty liver formation require in-depth exploration, and corresponding therapeutic strategies are urgently needed. Here, through serological testing of mice with fatty liver, it is found that the rhythms of prolactin secretion are disturbed and that the circulating prolactin level is reduced. Based on these findings, prolactin's biological effects on fatty liver are investigated, and biomimetic photothermal-responsive core-shell microneedles with periodically prolactin releasing are proposed to inhibit lipid accumulation in liver. The microneedles are comprised of poly(lactic-co-glycolic acid) shells and prolactin-loaded cores of photothermal black phosphorus, phase-change gelatin, and carrageenan. Under periodically stimulation of near infrared (NIR), the prolactin in the microneedles can be released in a rhythmic manner for inhibiting the lipid accumulation in liver cells. Based on these features, it is demonstrated in mice with fatty liver that the bioinspired-responsive microneedles can facilitate prolactin mitigating hepatic steatosis through its interaction with the hepatic prolactin receptor (PRLR) and by modulating the expression of fatty acid translocase (FAT/CD36). Thus, these photothermal-responsive core-shell microneedles with prolactin pulse release hold significant promise for the treatment of fatty liver disease.