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Red blood cells-hitchhiking mediated pulmonary delivery of ivermectin: effects of nanoparticles properties.

Authors
  • Zheng, Jinpeng1
  • Lu, Caihong2
  • Ding, Yaning3
  • Zhang, Jinbang4
  • Tan, Fangyun2
  • Liu, Jingzhou1
  • Yang, Guobao1
  • Wang, Yuli1
  • Li, Zhiping1
  • Yang, Meiyan1
  • Yang, Yang1
  • Gong, Wei1
  • Gao, Chunsheng5
  • 1 State key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China. , (China)
  • 2 State key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China; School of Pharmacy, Guangxi Medical University, Nanning, 530021, PR China. , (China)
  • 3 State key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China; School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Benxi 117004, PR China. , (China)
  • 4 State key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China; College of Pharmacy, Henan University, Kaifeng, 475000, PR China. , (China)
  • 5 State key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
International journal of pharmaceutics
Publication Date
Apr 04, 2022
Pages
121719–121719
Identifiers
DOI: 10.1016/j.ijpharm.2022.121719
PMID: 35390488
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Recent studies have demonstrated that ivermectin (IVM) exhibits antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of coronavirus disease (COVID-19). However, the repurposing of IVM for treatment of COVID-19 has presented challenges primarily due to the low IVM plasma concentration after oral administration, which was well below IC50. Here, a red blood cells (RBCs)-hitchhiking strategy was used for the targeted delivery of IVM-loaded nanoparticles to the lung. IVM-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (IVM-PNPs) and chitosan-coating IVM-PNPs (IVM-CSPNPs) were prepared and adsorbed onto RBCs. Both RBCs-hitchhiked IVM-PNPs and IVM-CSPNPs could significantly enhance IVM delivery to lungs, improve IVM accumulation in lung tissue, inhibit the inflammatory responses and finally significantly alleviate the progression of acute lung injury. Specifically, the redistribution and circulation effects were related to the properties of nanoparticles (NPs). RBCs-hitchhiked cationic IVM-CSPNPs showed longer circulation time, slower accumulation and elimination rates, and higher anti-inflammatory activity than RBCs-hitchhiked anionic IVM-PNPs. Therefore, RBC-hitchhiking provides an alternative strategy to improve IVM pharmacokinetics and bioavailability for repurposing of IVM to treat COVID-19. Furthermore, according to different redistribution effects of different NPs, RBCs-hitchhiked NPs may achieve various accumulation rates and circulation times for different requirements of drug delivery. Copyright © 2022. Published by Elsevier B.V.

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