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

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...

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Main Authors: Fang Wang, Yu Deng, Luying Yu, Ao Zhou, Jieting Wang, Jingyan Jia, Ning Li, Fadian Ding, Wei Lian, Qicai Liu, Yu Yang, Xinhua Lin
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/14/11/2341
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author Fang Wang
Yu Deng
Luying Yu
Ao Zhou
Jieting Wang
Jingyan Jia
Ning Li
Fadian Ding
Wei Lian
Qicai Liu
Yu Yang
Xinhua Lin
author_facet Fang Wang
Yu Deng
Luying Yu
Ao Zhou
Jieting Wang
Jingyan Jia
Ning Li
Fadian Ding
Wei Lian
Qicai Liu
Yu Yang
Xinhua Lin
author_sort Fang Wang
collection DOAJ
description 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.
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spelling doaj.art-98fa21a472194eb18556f1eb2ee47fd42023-11-24T06:20:40ZengMDPI AGPharmaceutics1999-49232022-10-011411234110.3390/pharmaceutics14112341A Macrophage Membrane–Polymer Hybrid Biomimetic Nanoplatform for Therapeutic Delivery of Somatostatin Peptide to Chronic PancreatitisFang Wang0Yu Deng1Luying Yu2Ao Zhou3Jieting Wang4Jingyan Jia5Ning Li6Fadian Ding7Wei Lian8Qicai Liu9Yu Yang10Xinhua Lin11College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, ChinaKey Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, ChinaKey Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, ChinaKey Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, ChinaKey Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, ChinaKey Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, ChinaKey Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, ChinaCenter for Reproductive Medicine, 1st Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou 350005, ChinaCenter for Reproductive Medicine, 1st Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou 350005, ChinaCenter for Reproductive Medicine, 1st Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou 350005, ChinaDepartment of Hepatopancreatobiliary Surgery, The Third Affiliated Hospital of Soochow University, Juqian Road 185, Changzhou 213000, ChinaKey Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, ChinaThe 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.https://www.mdpi.com/1999-4923/14/11/2341peptide deliverychronic pancreatitissomatostatinmacrophage membranebiomimetic nanoparticles
spellingShingle Fang Wang
Yu Deng
Luying Yu
Ao Zhou
Jieting Wang
Jingyan Jia
Ning Li
Fadian Ding
Wei Lian
Qicai Liu
Yu Yang
Xinhua Lin
A Macrophage Membrane–Polymer Hybrid Biomimetic Nanoplatform for Therapeutic Delivery of Somatostatin Peptide to Chronic Pancreatitis
Pharmaceutics
peptide delivery
chronic pancreatitis
somatostatin
macrophage membrane
biomimetic nanoparticles
title A Macrophage Membrane–Polymer Hybrid Biomimetic Nanoplatform for Therapeutic Delivery of Somatostatin Peptide to Chronic Pancreatitis
title_full A Macrophage Membrane–Polymer Hybrid Biomimetic Nanoplatform for Therapeutic Delivery of Somatostatin Peptide to Chronic Pancreatitis
title_fullStr A Macrophage Membrane–Polymer Hybrid Biomimetic Nanoplatform for Therapeutic Delivery of Somatostatin Peptide to Chronic Pancreatitis
title_full_unstemmed A Macrophage Membrane–Polymer Hybrid Biomimetic Nanoplatform for Therapeutic Delivery of Somatostatin Peptide to Chronic Pancreatitis
title_short A Macrophage Membrane–Polymer Hybrid Biomimetic Nanoplatform for Therapeutic Delivery of Somatostatin Peptide to Chronic Pancreatitis
title_sort macrophage membrane polymer hybrid biomimetic nanoplatform for therapeutic delivery of somatostatin peptide to chronic pancreatitis
topic peptide delivery
chronic pancreatitis
somatostatin
macrophage membrane
biomimetic nanoparticles
url https://www.mdpi.com/1999-4923/14/11/2341
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