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.

Advances in biomimetic nanomaterial delivery systems: harnessing nature's inspiration for targeted drug delivery

“…Therefore, MM-encapsulated nano-DDSs have emerged as a promising solution for drug delivery challenges in inflammatory diseases. [50][51][52][53][54][55][56][57][58] Wang et al 59 developed a MMcoated poly(lactic-co-glycolic acid) (PLGA) nano-delivery system to enhance the bioavailability of growth inhibitor (SST) peptides for the treatment of chronic pancreatitis. The NPs were biocompatible and targetable to activate endothelial cells in vitro.…”

“…5 The macrophage membrane-coated PLGA NPs loaded with the SST peptide for the treatment of chronic pancreatitis. 59 Reproduced from ref. 59 with permission from Pharmaceutics, copyright 2022.…”

Cell Membrane‐Coated Nanoparticles: A New Frontier in Immunomodulation

“…[138] A noteworthy shift in recent times has been the adoption of commercial kits for membrane isolation, particularly in the context of EVs, as evident in the scientific literature. [139] Nevertheless, the significant expense associated with these kits may pose scalability challenges in both research and production domains.…”

“…In addition, DLS and zeta potential measurements can be combined to serve as a preliminary test to ascertain the colloidal stability of CMCNs over extended storage periods. [139] Microscopic analysis techniques, including transmission electron microscopy (TEM), offer valuable insights into these systems. TEM allows for the visualization of the core-shell structure of coated NPs.…”

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