Biomimetic Nanoparticles Loaded with Ulinastatin for the Targeted Treatment of Acute Pancreatitis

Mol Pharm. 2023 Aug 7;20(8):4108-4119. doi: 10.1021/acs.molpharmaceut.3c00238. Epub 2023 Jun 22.

Abstract

Ulinastatin is commonly used in the clinic to treat acute pancreatitis (AP), but its therapeutic effect was limited by the presence of the blood-pancreas barrier (BPB) and low specificity. Here, we prepared a macrophage biomimetic nanoparticle (MU) that delivered ulinastatin to address the above issues. Macrophage membrane was used as a shell for a mixture of PEG-PLGA and ulinastatin. It was found that MU showed good stability and biocompatibility in vitro and in vivo. According to in vivo fluorescence imaging, MU displayed a great inflammation targeting effect both in a subcutaneous inflammation model and in situ pancreatitis mouse model, which was ascribed to the presence of adhesion proteins. In vitro and in vivo results demonstrated that MU have a superior AP treatment effect by inhibiting pro-inflammatory factors and keeping cells viability. It was suggested the MU could provide a new strategy for targeted AP treatment.

Keywords: acute pancreatitis; blood−pancreas barrier; macrophage membrane; targeted therapy; ulinastatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Biomimetics
  • Inflammation
  • Mice
  • Nanoparticles*
  • Pancreatitis* / drug therapy

Substances

  • urinastatin