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Manuscript ID : JMW-2104-1969 (R1) Visit : 154 Page: 119 - 133

10.30495/jmw.2022.1928771.1969

20.1001.1.20083068.1401.15.0.9.1

Article Type: Original Research

In Vitro Evaluation of Optimized Diphtheria and Tetanus Toxoids Loaded Alginate Nanoparticles

Subject Areas : Microbial Biotechnology

Simin Hosseini 1 (PhD candidate, Department of Microbiology, Faculty of Biology, Karaj Branch, Islamic Azad University, Karaj, Iran.)
Mojtaba Noofeli 2 (Associate Professor, Department of Human Bacterial Vaccines Production, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj 3197619751, Iran.)
Mahrooz Dezfulian 3 (Assistant Professor, Department of Microbiology, Faculty of Biology, Karaj Branch, Islamic Azad University, Karaj, Iran.)
Hamidreza Goudarzi 4 (Central Laboratory, Razi Vaccine, and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran.)
Zahra Salehi Najafabadi 5 (Central laboratory, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran)

Received: 2022-04-29 Accepted : 2022-08-26 Published : 2022-09-06

Keywords: Adjuvant, Zeta Potential, Diphtheria toxoid, co-deliver, loading efficiency,

Abstract :

Background and objective: Diphtheria and tetanus vaccine contains a high quantity of aluminum as an adjuvant potential to affect the nervous system, particularly in infants with kidney disease. Thus, the focus of this study was on in vitro preparation and evaluation to co-deliver DT toxoids by loading on alginate nanoparticles (NPs) as a non-toxic substance without antigenicity.Materials and Methods: Using the gel-ionization method, alginate NPs samples were prepared and characterized in respect of size, zeta potential, and polydispersity index (PDI). The effects of     alginate concentrations, calcium chloride, and Poly Lysine and the stirring time and speed in     addition to the loading efficiency, loading capacity, and in vitro release profile were assessed.Results: The optimized NPs were prepared at a concentration of 0.02 %w/v sodium alginate, 0.1 %w/v calcium chloride, and 0.04% w/v Poly L-Lysine during 45 minutes of stirring at 1300 rpm. They also had a mean particle size <150 nm with a mean PDI of around 0.5. The appropriate  loading efficiency was obtained at a concentration of loaded toxoids similar to a conventional DT vaccine, which resulted in the prolonged release of about 85% of loaded toxoids over 120 hours. The SDS-PAGE and dot-blot confirmed the stability and antigenic activity of the released toxoids.Conclusion: These results can significantly contribute to further developing alginate NPs          containing DT toxoids in optimized in vitro conditions as a platform for in vivo evaluation to achieve a promising vehicle for immunization of infants and children against diphtheria and      tetanus. 

References:

 

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31.Dórea JG. Exposure to mercury and aluminum in early life: developmental vulnerability as a modifying factor in neurologic and immunologic effects. Int J Env Res Public Health. 2015;12(2):1295-313.

  1. Tarhini M, Benlyamani I, Hamdani S, Agusti G, Fessi H, Greige-Gerges H, et al. Protein-based nanoparticle preparation via nanoprecipitation method. Materials. 2018;11(3):394.
    2.
  2. Moradi Bidhendi S, Zolfagharian H, Mohamadpour Dounighi N, Saraei F, Khaki P, Inanlou F. Design and evaluate alginate nanoparticles as a protein delivery system. Arch Razi Inst. 2013;68(2):139-46.
    3.
  3. Ferreiro MG, Tillman L, Hardee G, Bodmeier R. Characterization of alginate/poly-L-lysine particles as antisense oligonucleotide carriers. Int J Pharm. 2002;239(1-2):47-59.
    4.
  4. Modi K, Bhalodia J, Pathak T, Raval P, Pansara P, Vasoya N, et al. Bimodal to Unimodal Particle Size Distribution Transformation in Nanocrystalline Cobalt–Ferri–Chromites. Int J Sci Res Physic Appl Sci. 2018;6:32-6.
    5.
  5. Chamundeeswari M, Jeslin J, Verma ML. Nanocarriers for drug delivery applications. Environ Chem Lett. 2019;17(2):849-65.
    6.
  6. Dahman Y. Nanotechnology and Functional Materials for Engineers. Amsterdam. Elsevier. 2017.
    7.
  7. Vila A, Sánchez A, Janes K, Behrens I, Kissel T, Jato JLV, et al. Low molecular weight chitosan nanoparticles as new carriers for nasal vaccine delivery in mice. Eur J Pharm Biopharm. 2004;57(1):123-31.
    8.
  8. Mortazavi SAR, Rezaei MA. Preparation and evaluation of diphtheria toxoid-containing microspheres. Ir J Pharm Sci. 2004; 3(3): 133-143.
    9.

 

_||_

 

.1 Rafiqi SI, Kumar S, Zehra A, Kumar D, Jain S, Sethi K, et al. Nanovaccinology: Dawn of biomimetic vaccine carriers. J Entomol Zool Stud. 2017; 5(2): 795-802 2017.

  1. Apostólico JdS, Lunardelli VAS, Coirada FC, Boscardin SB, Rosa DS. Adjuvants: classification, modus operandi, and licensing. J Immunol Res. 2016;2016.
    2.
  2. Prashant CK, Kumar M, Dinda AK. Nanoparticle based tailoring of adjuvant function: the role in vaccine development. J Biomed Nanotechnol. 2014;10(9):2317-31.
    3.
  3. Tomljenovic L, Shaw C. Mechanisms of aluminum adjuvant toxicity and autoimmunity in pediatric populations. Lupus. 2012;21(2):223-30.
    4.
  4. Principi N, Esposito S. Aluminum in vaccines: Does it create a safety problem? Vaccine. 2018;36(39):5825-31.
    5.
  5. Esposito S, Mastrolia MV, Prada E, Pietrasanta C, Principi N. Vaccine administration in children with chronic kidney disease. Vaccine. 2014;32(49):6601-6.
    6.
  6. Chen Y-C, Cheng H-F, Yang Y-C, Yeh M-K. Nanotechnologies applied in biomedical vaccines. Micro and Nanotechnologies for Biotechnology. Stanciu SG. London. IntechOpen. (2016): 84-105.
    7.
  7. Lung P, Yang J, Li Q. Nanoparticle formulated vaccines: opportunities and challenges. Nanoscale. 2020;12(10):5746-63.
    8.
  8. Ching SH, Bansal N, Bhandari B. Alginate gel particles–A review of production techniques and physical properties. Crit Rev Food Sci Nutr. 2017;57(6):1133-52.
    9.
  9. Rajaonarivony M, Vauthier C, Couarraze G, Puisieux F, Couvreur P. Development of a New Drug Carrier Made from Alginate. J Pharm Sci. 1993;82(9):912-7.
    10.
  10. Matsumoto H, Haniu H, Komori N. Determination of Protein Molecular Weights on SDS-PAGE. In: Kurien BT, Scofield RH, editors. Electrophoretic Separation of Proteins: Methods and Protocols. New York, Springer. (2019): 101-5.
    11.
  11. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72(1):248-54.
    12.
  12. Rezaei MA, Mortazavi S, Mohammadpour DN, Zou AH, Alonso M. Preparation and in-vitro evaluation of sodium alginate microspheres containing diphtheria toxoid as new vaccine delivery. Arch Razi Inst. 2008; (2):19-28. 14. Papadimitriou S, Bikiaris D, Avgoustakis K, Karavas E, Georgarakis M. Chitosan nanoparticles loaded with dorzolamide and pramipexole. Carbohydr Polym. 2008;73(1):44-54.
    13.
  13. Draget KI, Taylor C. Chemical, physical and biological properties of alginates and their biomedical implications. Food Hydrocoll. 2011;25(2):251-6.
    14.
  14. Silva CM, Ribeiro AJ, Figueiredo IV, Gonçalves AR, Veiga F. Alginate microspheres prepared by internal gelation: Development and effect on insulin stability. Int J Pharm. 2006;311(1-2):1-10.
    15.
  15. Alfatama M, Lim LY, Wong TW. Alginate–C18 conjugate nanoparticles loaded in tripolyphosphate-cross-linked chitosan–oleic acid conjugate-coated calcium alginate beads as oral insulin carrier. Mol Pharm. 2018;15(8):3369-82.
    16.
  16. Ghaderinia P, Shapouri R. Assessment of immunogenicity of alginate microparticle containing Brucella melitensis 16M oligo polysaccharide tetanus toxoid conjugate in mouse. Banat's J Biotechnol. 2017;8(16):83-92.
    17.
  17. Azimi S, Safari Zanjani L. Immunization against Pseudomonas aeruginosa using Alg-PLGA nano-vaccine. Ir J Basic Med Sci. 2021; 476-482.
    18.
  18. Pandey R, Khuller G. Polymer based drug delivery systems for mycobacterial infections. Curr Drug Deliv. 2004;1(3):195-201.
    19.
  19. Lin S-F, Chen Y-C, Chen R-N, Chen L-C, Ho H-O, Tsung Y-H, et al. Improving the stability of astaxanthin by microencapsulation in calcium alginate beads. PLoS One. 2016;11(4):e0153685.
    20.
  20. Tsai S, Ting Y. Synthesize of alginate/chitosan bilayer nanocarrier by CCD-RSM guided co-axial electrospray: A novel and versatile approach. Food Res Int. 2019;116:1163-72.
    21.
  21. González Ferreiro M, Tillman L, Hardee G, Bodmeier R. Characterization of alginate/ poly-L-lysine particles as antisense oligonucleotide carriers. Int J Pharm. 2002;239(1-2):47-59.
    22.
  22. Sarei F, Dounighi NM, Zolfagharian H, Khaki P, Bidhendi SM. Alginate nanoparticles as a promising adjuvant and vaccine delivery system. Indian J Pharm Sci. 2013;75(4):442.
    23.
  23. Dobakhti F, Rahimi F, Dehpour AR, Taghikhani M, Ajdary S, Rafiei S, et al. Stabilizing effects of calcium alginate microspheres on Mycobacterium bovis BCG intended for oral vaccination. J Microencapsul. 2006;23(8):844-54.26. Zimet P, Mombrú ÁW, Faccio R, Brugnini G, Miraballes I, Rufo C, et al. Optimization and characterization of nisin-loaded    alginate-chitosan nanoparticles with antimicrobial activity in lean beef. LWT. 2018;91:107-16.
    24.
  24. Baghbani F, Moztarzadeh F, Mohandesi JA, Yazdian F, Mokhtari-Dizaji M, Hamedi S. Formulation design, preparation and characterization of multifunctional alginate stabilized nanodroplets. Int J Biol Macromol. 2016;89:550-8.
    25.
  25. Goudarzi HR, Mokarram A, Noofeli M, Shirvan A, Saadati M. Preparation and evaluation of alginate nanoparticles containing pertussis toxin as a particulate delivery system. Int J Adv Biotechnol Res. 2016;7(2):558-64.
    26.
  26. Woitiski CB, Veiga F, Ribeiro A, Neufeld R. Design for optimization of nanoparticles integrating biomaterials for orally dosed insulin. Eur J Pharm Biopharm. 2009;73(1):25-33.
    27.
  27. Woitiski CB, Neufeld RJ, Ribeiro AJ, Veiga F. Colloidal carrier integrating biomaterials for oral insulin delivery: influence of component formulation on physicochemical and biological parameters. Acta Biomater. 2009;5(7):2475-84.
    28.

31.Dórea JG. Exposure to mercury and aluminum in early life: developmental vulnerability as a modifying factor in neurologic and immunologic effects. Int J Env Res Public Health. 2015;12(2):1295-313.

  1. Tarhini M, Benlyamani I, Hamdani S, Agusti G, Fessi H, Greige-Gerges H, et al. Protein-based nanoparticle preparation via nanoprecipitation method. Materials. 2018;11(3):394.
    2.
  2. Moradi Bidhendi S, Zolfagharian H, Mohamadpour Dounighi N, Saraei F, Khaki P, Inanlou F. Design and evaluate alginate nanoparticles as a protein delivery system. Arch Razi Inst. 2013;68(2):139-46.
    3.
  3. Ferreiro MG, Tillman L, Hardee G, Bodmeier R. Characterization of alginate/poly-L-lysine particles as antisense oligonucleotide carriers. Int J Pharm. 2002;239(1-2):47-59.
    4.
  4. Modi K, Bhalodia J, Pathak T, Raval P, Pansara P, Vasoya N, et al. Bimodal to Unimodal Particle Size Distribution Transformation in Nanocrystalline Cobalt–Ferri–Chromites. Int J Sci Res Physic Appl Sci. 2018;6:32-6.
    5.
  5. Chamundeeswari M, Jeslin J, Verma ML. Nanocarriers for drug delivery applications. Environ Chem Lett. 2019;17(2):849-65.
    6.
  6. Dahman Y. Nanotechnology and Functional Materials for Engineers. Amsterdam. Elsevier. 2017.
    7.
  7. Vila A, Sánchez A, Janes K, Behrens I, Kissel T, Jato JLV, et al. Low molecular weight chitosan nanoparticles as new carriers for nasal vaccine delivery in mice. Eur J Pharm Biopharm. 2004;57(1):123-31.
    8.
  8. Mortazavi SAR, Rezaei MA. Preparation and evaluation of diphtheria toxoid-containing microspheres. Ir J Pharm Sci. 2004; 3(3): 133-143.
    9.

 

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