Inflammation-Targeted Delivery of Celastrol via Neutrophil Membrane-Coated Nanoparticles in the Management of Acute Pancreatitis

• DOI: 10.1021/acs.molpharmaceut.8b01342
• Publication Date: 2019-02-12T22:43:47Z
• Authors: Xu Zhou; Xi Cao; He Tu; Zhi-Rong Zhang; Li Deng
• Keywords: Inflammation; Male; 0301 basic medicine; 0303 health sciences; Interleukin-6; Neutrophils; Polyesters; Cell Membrane; Lung Injury; Polyethylene Glycols; Rats; 3. Good health; Rats, Sprague-Dawley; Disease Models, Animal; 03 medical and health sciences; Pancreatitis; Amylases; Animals; Nanoparticles; Tissue Distribution; Molecular Targeted Therapy; Particle Size; Pharmaceutical Vehicles; Pentacyclic Triterpenes

Celastrol (CLT)-loaded PEG-PLGA nanoparticles (NPs/CLT) coated with neutrophil membranes (NNPs/CLT) were explored for the management of acute pancreatitis (AP). PEG-PLGA nanoparticles sized around 150 nm were proven to selectively accumulate in the pancreas in rats with AP. NNPs were found to overcome the blood-pancreas barrier and specifically distributed to the pancreatic tissues. Moreover, NNPs showed more selective accumulation in the pancreas than nanoparticles without any membrane coating in AP rats. Compared to CLT solution and the NPs/CLT group, NNPs/CLT significantly downregulated the levels of serum amylase and pancreatic myeloperoxidase in AP rats. Also, using NNPs as the delivery vehicle significantly reduced the systemic toxicity of CLT in AP rats. Together, these results suggest that NNPs/CLT represent a highly promising delivery vehicle for the targeted therapy of AP.