Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Stealth Nanogels of Histinylated Poly Ethyleneimine for Sustained Delivery of Methotrexate in Collagen-Induced Arthritis Model Publisher Pubmed



Abolmaali S1 ; Tamaddon A1 ; Kamalisarvestani E2 ; Ashraf M3 ; Dinarvand R4
Authors
Show Affiliations
Authors Affiliations
  1. 1. Center for Nanotechnology in Drug Delivery, Department of Pharmaceutical Nanotechnology, Shiraz University of Medical Sciences, Shiraz, 71345, Iran
  2. 2. Autoimmune Diseases Research Center, School of Medicine, Department of Immunology, Shiraz University of Medical Sciences, Shiraz, 71345, Iran
  3. 3. Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, 71345, Iran
  4. 4. Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 14174, Iran

Source: Pharmaceutical Research Published:2015


Abstract

Purpose: The study aimed to illustrate application of polycation Stealth nanogels for sustained delivery of methotrexate (MTX) in collagen induced arthritis (CIA) model in C57Bl/6 mice. Methods: Nanogel synthesis involves metal ion coordinated self-assembly of PEGylated poly ethyleneimine (L-histidine substituted), chemical crosslinking and subsequent removal of the coordinated metal. The nanogels were characterized by TEM and DLS-zeta potential. Comparative efficacy and pharmacokinetics of the i.v. administred MTX-loaded nanogels were investigated in the CIA model. Inflammation site passive accumulation of the fluorophore-labeled nanogels was tested using in-vivo imaging of mice paw received unilateral injection of lipopolysaccharide. Results: Uniform nanogels (sizes ~40 nm by TEM) were loaded with MTX (entrapment efficiency∈=∈62% and drug loading∈=∈54% at the MTX feeding ratio of 0.3 relative to total molar concentration of the polymer amines). The nanogels exhibited neutral surface charge and an acceptable biocompatibility in terms of albumin aggregation, hemolysis, erythrocyte aggregation and cytotoxicity. Single dose pharmacokinetics of the MTX-loaded nanogels, unlike free drug, showed a sustained plasma profile. When arthritis established as confirmed by histopathology, a remarkable decline of paw swelling and clinical scores was observed. Fluorescence intensity of the nanogels was enhanced about 2.7 folds at the inflamed than control normal ankle. Conclusion: Sustained delivery of MTX and preferential accumulation of the nanogels in inflamed paw might explain the superior clinical outcome of the MTX-loaded nanogels. © 2015 Springer Science+Business Media New York.
Related Docs
1. Chemically Crosslinked Nanogels of Pegylated Poly Ethyleneimine (L-Histidine Substituted) Synthesized Via Metal Ion Coordinated Self-Assembly for Delivery of Methotrexate: Cytocompatibility, Cellular Delivery and Antitumor Activity in Resistant Cells, Materials Science and Engineering C (2016)
2. Block Ionomer Micellar Nanoparticles From Double Hydrophilic Copolymers, Classifications and Promises for Delivery of Cancer Chemotherapeutics, European Journal of Pharmaceutical Sciences (2017)
3. Effect of Pegylation on Assembly Morphology and Cellular Uptake of Poly Ethyleneimine-Cholesterol Conjugates for Delivery of Sorafenib Tosylate in Hepatocellular Carcinoma, BioImpacts (2018)
4. Fabrication and in Vitro Evaluation of Magnetic Plga Nanoparticles As a Potential Methotrexate Delivery System for Breast Cancer, Journal of Drug Delivery Science and Technology (2018)
5. Smart Internal Stimulus-Responsive Nanocarriers for Drug and Gene Delivery, Smart internal stimulus-responsive nanocarriers for drug and gene delivery (2015)
6. Methotrexate-Conjugated Quantum Dots: Synthesis, Characterisation and Cytotoxicity in Drug Resistant Cancer Cells, Journal of Drug Targeting (2016)
Experts (# of related papers)
Rassoul Dinarvand (2)
Alimohammad Alizadeh (1)