A Macrophage Membrane–Polymer Hybrid Biomimetic Nanoplatform for Therapeutic Delivery of Somatostatin Peptide to Chronic Pancreatitis

Abstract

The clinical translation of therapeutic peptides is generally challenged by multiple issues involving absorption, distribution, metabolism and excretion. In this study, a macrophage membrane-coated poly(lactic-co-glycolic acid) (PLGA) nanodelivery system was developed to enhance the bioavailability of the somatostatin (SST) peptide, which faces the hurdles of short half-life and potential side effects in the treatment of chronic pancreatitis. Using a facile nanoprecipitation strategy, SST was loaded in the nanoparticles with an encapsulation efficiency (EE) and a loading efficiency (LE) of 73.68 ± 3.56% and 1.47 ± 0.07%, respectively. The final formulation of SST-loaded nanoparticles with the camouflage of macrophage membrane (MP-SST) showed a mean diameter of 151 ± 4 nm and an average zeta potential of −29.6 ± 0.3 mV, which were stable long term during storage. With an above 90% cell viability, a hemolysis level of about 2% (<5%) and a preference for being ingested by activated endothelial cells compared to macrophages, the membrane–polymer hybrid nanoparticle showed biocompatibility and targeting capability in vitro. After being intravenously administered to mice with chronic pancreatitis, the MP-SST increased the content of SST in the serum (123.6 ± 13.6 pg/mL) and pancreas (1144.9 ± 206.2 pg/g) compared to the treatment of (Dulbecco’s phosphate-buffered saline) DPBS (61.7 ± 6.0 pg/mL in serum and 740.2 ± 172.4 pg/g in the pancreas). The recovery of SST by MP-SST downregulated the expressions of chronic pancreatitis-related factors and alleviated the histologic severity of the pancreas to the greatest extent compared to other treatment groups. This augmentation of SST therapeutic effects demonstrated the superiority of integrating the synthetic polymer with biological membranes in the design of nanoplatforms for advanced and smart peptide delivery. Other peptides like SST can also be delivered via the membrane–polymer hybrid nanosystem for the treatment of diseases, broadening and promoting the potential clinical applications of peptides as therapeutics.

Keywords

• peptide delivery
• chronic pancreatitis
• somatostatin
• macrophage membrane
• biomimetic nanoparticles