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Development and Physicochemical, Toxicity and Immunogenicity Assessments of Recombinant Hepatitis B Surface Antigen (Rhbsag) Entrapped in Chitosan and Mannosylated Chitosan Nanoparticles: As a Novel Vaccine Delivery System and Adjuvant Publisher Pubmed



Mehrabi M1 ; Dounighi NM2 ; Rezayat Sorkhabadi SM1, 3 ; Doroud D4 ; Amani A1 ; Khoobi M5, 6 ; Ajdary S7 ; Pilehvarsoltanahmadi Y8
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Authors Affiliations
  1. 1. Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran
  3. 3. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Regulatory Department, Production and Research Complex, Pasteur Institute of Iran, Tehran, Iran
  5. 5. Nanobiomaterials Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Immunology, Pasteur Institute of Iran, Tehran, Iran
  8. 8. Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran

Source: Artificial Cells# Nanomedicine and Biotechnology Published:2018


Abstract

In this study chitosan nanoparticles (CS NPs) and mannosylated chitosan nanoparticles (MCH NPs) loaded with recombinant hepatitis B surface antigen (rHBsAg) was synthesized as a vaccine delivery system and assessed toxically and immunologically. The physicochemical properties of the nanoparticles (NPs) were determined by methods including scanning electron microscope (SEM) and dynamic light scattering (DLS). The morphology of the NPs was semi spherical and the average diameter of the loaded CS and MCH NPs was found to be 189 and 239 nm, respectively. The release studies showed that after the initial burst, both of the loaded NPs provided a continuous and slow release of the antigens. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed concentration and time dependent toxicity profile for both formulations, but rHBsAg loaded CS nanoparticle showed higher toxicity due to smaller particle size and larger zeta potential. Abnormal toxicity test (ATT) results showed no signs of toxicity in mice and guinea-pigs treated with loaded MCHNPs. Stability test for six months showed acceptable changes in size, surface charge, and antigenicity for loaded MCH nanoparticles. Finally, in vivo immunogenicity study revealed greater adjuvant capability of MCH nanoparticles than others formulations. Our results showed MCH NPs can be used as a controlled and targeted vaccine delivery system. © 2017, © 2017 Informa UK Limited, trading as Taylor & Francis Group.
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