Development of a Combined Enterosorbent Based on Silicon Dioxide with Immobilized Antitoxic Antibodies for Specific Prophylaxis of Escherichiosis in Young Animals

Relevance. This review addresses the current challenge of preventing and treating bacterial gastrointestinal infections in young farm animals, specifically escherichiosis. Conventional therapy, including the parenteral administration of hyperimmune sera, has limited efficacy due to insufficient delivery of antitoxic antibodies to the intestinal lumen. The development of next-generation combined enterosorbents, which integrate the properties of a carrier and a specific antitoxin, is considered a promising alternative.

Methods. The work presents an analysis of modern approaches to modifying sorbent surfaces for the immobilization of biologically active molecules. Particular attention is paid to chemical functionalization based on silanization using 3-aminopropyltriethoxysilane (APTES) as a method that ensures the formation of stable covalent bonds between the silicon dioxide surface and antibodies. Information on existing classes of enterosorbents used in animal husbandry is summarized, and the choice of highly dispersed silicon dioxide as an optimal platform for creating a targeted drug is justified.

Results. The practical significance of the work lies in the scientific rationale for an approach to creating an innovative agent for the specific prophylaxis of escherichiosis. This agent will provide targeted delivery and prolonged activity of antitoxic antibodies directly at the site of infection, thereby helping to reduce economic losses in animal husbandry.

1. Peraro MD, van der Goot F.G. Pore-forming toxins: ancient, but never really out of fashion. Nature Reviews Microbiology. 2016; 14: 77–92.https://doi.org/10.1038/nrmicro.2015.3

2. Dettmeyer R.B. Histopathology of Selected Trauma. Dettmeyer R.B. Forensic Histopathology. Fundamentals and Perspectives. Cham: Springer. 2018; 47–83.https://doi.org/10.1007/978-3-319-77997-3_3

3. Shetty S.S. et al. Environmental pollutants and their effects on human health. Heliyon. 2023; 9(9): e19496.https://doi.org/10.1016/j.heliyon.2023.e19496

4. Qu X., Gou M., Zaidan J., Zhang K., Chen S. Challenges and Opportunities in Developing Nanoparticles for Detoxification. Nanomedicine. 2014; 9(16): 2437–2439.https://doi.org/10.2217/nnm.14.168

5. Muhammad F., Nguyen T.D.T., Raza A., Akhtar B., Aryal S. A review on nanoparticle-based technologies for biodetoxification. Drug and Chemical Toxicology. 2017; 40(4): 489–497.https://doi.org/10.1080/01480545.2016.1277736

6. Lam K.-h. et al. Structural Insights into Rational Design of SingleDomain Antibody-Based Antitoxins against Botulinum Neurotoxins. Cell Reports. 2020; 30(8): 2526–2539.https://doi.org/10.1016/j.celrep.2020.01.107

7. Manikandan P. et al. Identification, functional characterization, assembly and structure of ToxIN type III toxin–antitoxin complex from E. coli. Nucleic Acids Research. 2022; 50(3): 1687–1700.https://doi.org/10.1093/nar/gkab1264

8. Kim J., De Jesus O. Medication routes of administration. Treasure Island: StatPearls. 2023.

9. Chan W.T., Balsa D., Espinosa M. One cannot rule them all: Are bacterial toxins-antitoxins druggable?. FEMS Microbiology Reviews. 2015; 39(4): 522–540.https://doi.org/10.1093/femsre/fuv002

10. Diamant E., Torgeman A., Ozeri E., Zichel R. Monoclonal Antibody Combinations that Present Synergistic Neutralizing Activity: A Platform for Next-Generation Anti-Toxin Drugs. Toxins. 2015; 7(6): 1854–1881.https://doi.org/10.3390/toxins7061854

11. Augustine R., Hasan A., Primavera R., Wilson R.J., Thakor A.S., Kevadiya B.D. Cellular uptake and retention of nanoparticles: Insights on particle properties and interaction with cellular components. Materials Today Communications. 2020; 25: 101692.https://doi.org/10.1016/j.mtcomm.2020.101692

12. Desai N., Pande S., Salave S., Singh T.R.R., Vora L.K. Antitoxin nanoparticles: design considerations, functional mechanisms, and applications in toxin neutralization. Drug Discovery Today. 2024; 29(8): 104060.https://doi.org/10.1016/j.drudis.2024.104060

13. Chang Q. Colloid and Interface Chemistry for Water Quality Control. Academic Press. 2016; 264. ISBN 978-0-12-809315-3https://doi.org/10.1016/C2014-0-02506-3

14. Joudeh N., Linke D. Nanoparticle classification, physicochemical properties, characterization, and applications: a comprehensive review for biologists. Journal of Nanobiotechnology. 2022; 20: 262.https://doi.org/10.1186/s12951-022-01477-8

15. Murugan K., Choonara Y.E., Kumar P., Bijukumar D., du Toit L.C., Pillay V. Parameters and characteristics governing cellular internalization and trans-barrier trafficking of nanostructures. International Journal of Nanomedicine. 2015; 10(1): 2191–2206.https://doi.org/10.2147/IJN.S75615

16. Zhang D., Wei L., Zhong M., Xiao L., Li H.-W., Wang J. The morphology and surface charge-dependent cellular uptake efficiency of upconversion nanostructures revealed by single-particle optical microscopy. Chemical Science. 2018; 9(23): 5260–5269.https://doi.org/10.1039/C8SC01828F

17. Nishimoto‐Sauceda D., Romero‐Robles L.E., Antunes‐Ricardo M. Biopolymer nanoparticles: a strategy to enhance stability, bioavailability, and biological effects of phenolic compounds as functional ingredients. Journal of the Science of Food and Agriculture. 2022; 102(1): 41–52.https://doi.org/10.1002/jsfa.11512

18. Xu L., Wang X., Liu Y., Yang G., Falconer R.J., Zhao C.-X. Lipid Nanoparticles for Drug Delivery. Advanced NanoBiomed Research. 2022; 2(2): 2100109.https://doi.org/10.1002/anbr.202100109

19. Vora L., Tyagi M., Patel K., Gupta S., Vavia P. Self-assembled nanocomplexes of anionic pullulan and polyallylamine for DNA and pH-sensitive intracellular drug delivery. Journal of Nanoparticle Research. 2014; 16(12): 2781.https://doi.org/10.1007/s11051-014-2781-8

20. Liu Q., Kim Y.-J., Im G.-B., Zhu J., Wu Y., Liu Y., Bhang S.H. Inorganic Nanoparticles Applied as Functional Therapeutics. Advanced Functional Materials. 2021; 31(12): 2008171.https://doi.org/10.1002/adfm.202008171

21. Desai N., Chavda V., Singh T.R.R., Thorat N.D., Vora L.K. Cancer Nanovaccines: Nanomaterials and Clinical Perspectives. Small. 2024; 20(35): 2401631.https://doi.org/10.1002/smll.202401631

22. Phan H.T., Haes A.J. What Does Nanoparticle Stability Mean?. The Journal of Physical Chemistry C. 2019; 123(27): 16495–16507.https://doi.org/10.1021/acs.jpcc.9b00913

23. Khizar S. et al. Nanocarriers based novel and effective drug delivery system. International Journal of Pharmaceutics. 2023; 632: 122570.https://doi.org/10.1016/j.ijpharm.2022.122570

24. Polaka S., Desai N., Kshirsagar B., Rajpoot K., Tekade R.K. Revamping the pharmacokinetics of poorly soluble drugs using different formulations. Tekade R.K. (ed.). Biopharmaceutics and Pharmacokinetics Considerations. Academic Press. 2021; 1: 387–413.https://doi.org/10.1016/B978-0-12-814425-1.00005-X

25. Blum A.P., Kammeyer J.K., Rush A.M., Callmann C.E., Hahn M.E., Gianneschi N.C. Stimuli-Responsive Nanomaterials for Biomedical Applications. Journal of the American Chemical Society. 2015; 137(6): 2140–2154.https://doi.org/10.1021/ja510147n

26. Sheshala R., Madheswaran T., Panneerselvam J., Vora L., Thakur R.R.S. Stimuli-responsive nanomaterials in infectious diseases. Jain K., Ahmad J. (eds.). Nanotheranostics for Treatment and Diagnosis of Infectious Diseases. Academic Press. 2022; 151–198.https://doi.org/10.1016/B978-0-323-91201-3.00005-0

27. Chen W., Tian X., He W., Li J., Feng Y., Pan G. Emerging functional materials based on chemically designed molecular recognition. BMC Materials. 2020; 2: 1.https://doi.org/10.1186/s42833-019-0007-1

28. El Jundi A., Buwalda S.J., Bakkour Y., Garric X., Nottelet B. Double hydrophilic block copolymers self-assemblies in biomedical applications. Advances in Colloid and Interface Science. 2020; 283: 102213.https://doi.org/10.1016/j.cis.2020.102213

29. González-Jartín J.M. et al. Magnetic nanostructures for marine and freshwater toxins removal. Chemosphere. 2020; 256: 127019.https://doi.org/10.1016/j.chemosphere.2020.127019

30. Wieszczycka K., Staszak K., Woźniak-Budych M.J., Litowczenko J., Maciejewska B.M., Jurga S. Surface functionalization — The way for advanced applications of smart materials. Coordination Chemistry Reviews. 2021; 436: 213846.https://doi.org/10.1016/j.ccr.2021.213846

31. Manikkath J. et al. Nanoparticle-Mediated Active and Passive Drug Targeting in Oral Squamous Cell Carcinoma: Current Trends and Advances. Nanomedicine. 2023; 18(27): 2061–2080.https://doi.org/10.2217/nnm-2023-0247

32. Deci M.B., Liu M., Dinh Q.T., Nguyen J. Precision engineering of targeted nanocarriers. WIREs Nanomedicine and Nanobiotechnology. 2018; 10(5): e1511.https://doi.org/10.1002/wnan.1511

33. Bazban-Shotorbani S. et al. Revisiting structure-property relationship of pH-responsive polymers for drug delivery applications. Journal of Controlled Release. 2017; 253: 46–63.https://doi.org/10.1016/j.jconrel.2017.02.021

34. Mu Q. et al. Chemical Basis of Interactions Between Engineered Nanoparticles and Biological Systems. Chemical Reviews. 2014; 114(15): 7740–7781.https://doi.org/10.1021/cr400295a

35. Lunardi C.N., Gomes A.J., Rocha F.S., De Tommaso J., Patience G.S. Experimental methods in chemical engineering: Zeta potential. The Canadian Journal of Chemical Engineering. 2021; 99(3): 627–639.https://doi.org/10.1002/cjce.23914

36. Stoffelen C., Huskens J. Soft Supramolecular Nanoparticles by Noncovalent and Host–Guest Interactions. Small. 2016; 12(1): 96–119.https://doi.org/10.1002/smll.201501348

37. Vascon F. et al. Protein electrostatics: From computational and structural analysis to discovery of functional fingerprints and biotechnological design. Computational and Structural Biotechnology Journal. 2020; 18: 1774–1789.https://doi.org/10.1016/j.csbj.2020.06.029

38. Wen H., Jung H., Li X. Drug Delivery Approaches in Addressing Clinical Pharmacology-Related Issues: Opportunities and Challenges. The AAPS Journal. 2015; 17(6): 1327–1340.https://doi.org/10.1208/s12248-015-9814-9

39. Lu L.L., Suscovich T.J., Fortune S.M., Alter G. Beyond binding: antibody effector functions in infectious diseases. Nature Reviews Immunology. 2018; 18: 46–61.https://doi.org/10.1038/nri.2017.106

40. Zumbro E., Alexander-Katz A. Influence of Binding Site Affinity Patterns on Binding of Multivalent Polymers. ACS Omega. 2020; 5(19): 10774–10781.https://doi.org/10.1021/acsomega.0c00334

41. Erlendsson S., Teilum K. Binding Revisited—Avidity in Cellular Function and Signaling. Frontiers in Molecular Biosciences. 2020; 7: 615565.https://doi.org/10.3389/fmolb.2020.615565

42. Gupta V.K., Agarwal S., Ahmad R., Mirza A., Mittal J. Sequestration of toxic congo red dye from aqueous solution using ecofriendly guar gum/activated carbon nanocomposite. International Journal of Biological Macromolecules. 2020; 158: 1310–1318.https://doi.org/10.1016/j.ijbiomac.2020.05.025

43. Fang R.H., Luk B.T., Hu C.-M.J., Zhang L. Engineered nanoparticles mimicking cell membranes for toxin neutralization. Advanced Drug Delivery Reviews. 2015; 90: 69–80.https://doi.org/10.1016/j.addr.2015.04.001

44. Fierer J., Looney D., Kok M., Pechère J.-C. Nature and pathogenicity of micro-organisms. Cohen J.,Opal S.M., Powderly W.G. (eds.). Infectious Diseases. Third Edition. Mosby. 2010; 1: 3–29.https://doi.org/10.1016/B978-0-323-04579-7.00001-0

45. Manayani D.J. et al. A Viral Nanoparticle with Dual Function as an Anthrax Antitoxin and Vaccine. PLOS Pathogens. 2007; 3(10): e142.https://doi.org/10.1371/journal.ppat.0030142

46. Kulkarni A.A., Fuller C., Korman H., Weiss A.A., Iyer S.S. Glycan Encapsulated Gold Nanoparticles Selectively Inhibit Shiga Toxins 1 and 2. Bioconjugate Chemistry. 2010; 21(8): 1486–1493.https://doi.org/10.1021/bc100095w

47. Sarwar S, Ali A., Pal M., Chakrabarti P. Zinc oxide nanoparticles provide anti-cholera activity by disrupting the interaction of cholera toxin with the human GM1 receptor. The Journal of Biological Chemistry. 2017; 292(44): 18303–18311.https://doi.org/10.1074/jbc.m117.793240

48. Filippova O., Kiyko E., Zazulya A., Maslova N. Enterosorbent for farm animals. IOP Conference Series: Earth and Environmental Science. 2019; 403: 012142.https://doi.org/10.3390/medicina55090557

49. Sarnatskaya V. et al. The effect of two formulations of carbon enterosorbents on oxidative stress indexes and molecular conformation of serum albumin in experimental animals exposed to CCl4. Heliyon. 2020; 6(1): e03126.https://doi.org/10.1016/j.heliyon.2019.e03126

50. Tishin A.N., Pokrovskii M.V., Tishina O.M., Yakushev V.I., Zabolotskih N.V. Experimental study of the antidiarrhoeal activity of montmorillonite-containing enterosorbent. Kuban Scientific Medical Bulletin. 2017; (5): 82–89 (in Russian).https://doi.org/10.25207/1608-6228-2017-24-5-82-89

51. Wang M., Safe S., Hearon S.E., Phillips T.D. Strong adsorption of Polychlorinated Biphenyls by processed montmorillonite clays: Potential applications as toxin enterosorbents during disasters and floods. Environmental Pollution. 2019; 255(1): 113210.https://doi.org/10.1016/j.envpol.2019.113210

52. Zuev N. et al. Enterosorbent based on montmorillonite as a promising tool in the treatment and prevention of intestinal disorders in pigs. BIO Web of Conferences. 2021; 30: 02012.https://doi.org/10.1051/bioconf/20213002012

53. Kuznetsova S.A. et al. Enterosorbents from Abies Bark and their Therapeutic and Preventive Properties in Experimental Escherichiosis of Animals. Journal of Siberian Federal University. Chemistry. 2020; 13(1): 122–132 (in Russian).https://doi.org/10.17516/1998-2836-0158

54. Fatullayeva S., Tagiyev D., Zeynalov N. A review on enterosorbents and their application in clinical practice: Removal of toxic metals. Colloid and Interface Science Communications. 2021; 45: 100545.https://doi.org/10.1016/j.colcom.2021.100545

55. Howell C.A., Mikhalovsky S.V., Markaryan E.N., Khovanov A.V. Investigation of the adsorption capacity of the enterosorbent Enterosgel for a range of bacterial toxins, bile acids and pharmaceutical drugs. Scientific Reports. 2019; 9: 5629.https://doi.org/10.1038/s41598-019-42176-z

56. Kluczka J. Chitosan: Structural and Chemical Modification, Properties, and Application. International Journal of Molecular Sciences. 2024; 25(1): 554.https://doi.org/10.3390/ijms25010554

57. Shichkin V.P., Kurchenko O.V., Okhotnikova E.N., Chopyak V.V., Delfino D.V. Enterosorbents in complex therapy of food allergies: a focus on digestive disorders and systemic toxicity in children. Frontiers in Immunology. 2023; 14: 1210481.https://doi.org/10.3389/fimmu.2023.1210481

58. Brovko O. et al. Composite aerogel materials based on lignosulfonates and silica: Synthesis, structure, properties. Materials Chemistry and Physics. 2021; 269: 124768.https://doi.org/10.1016/j.matchemphys.2021.124768

59. Novokshonov A.A., Sokolova N.V. Enterosorption and its clinical effectiveness in complex treatment of acute intestinal infections in chil - dren. Current Pediatrics (Moscow). 2011; 10(1): 140–147 (in Russian).EDN NEJYTP

60. Tsikov A.V. Experience with enterosorption in the complex treatment of bronchial asthma. Vrachebnoye delo. 1986; (7): 35–37 (in Russian).EDN ROWTUX

61. Kormishina A.E., Mizina P.G., Solov’eva I.L. Pharmaceutical market of medicines of adsorptive action: state and prospects. Bashkortostan Medical Journal. 2018; 13(6): 55–62 (in Russian).EDN YXTXPV

62. Nikolayev V.G., Mikhalovsky S.V., Gurina N.M. Modern enterosorbents and mechanisms of their action. Efferentnaya terapiya. 2005; 11(4): 3–17 (in Russian).EDN WETVRL

63. Zhilyakova E.T., Bondarev A.V., Novikov O.O. Rational choice of enterosorbent based on its sorption-morphological characteristics. Meditsinskiy opponent. 2023;(3):59-64. EDN PZXAFS

64. Kucher S.V., Lototska O.V. Inclusion of enterosorbents in antiinflammatory therapy improve treatment effectiveness in COPD patients during exacerbations. The Ukrainian Biochemical Journal. 2021; 93(2): 107–114.https://doi.org/10.15407/ubj93.02.107

65. Naghshbandi M.P., Moghimi H. Stabilization of phytase on multiwalled carbon nanotubes via covalent immobilization. Methods in Enzymology. 2020; 630: 431–451.https://doi.org/10.1016/bs.mie.2019.10.013

66. Jenie S.N.A., Plush S.E., Voelcker N.H. Recent Advances on Luminescent Enhancement-Based Porous Silicon Biosensors. Pharmaceutical Research. 2016; 33(10): 2314–2336.https://doi.org/10.1007/s11095-016-1889-1

67. Rokicka-Konieczna P., Wanag A., Sienkiewicz A., Kusiak-Nejman E., Morawski A.W. Antibacterial effect of TiO2 nanoparticles modified with APTES. Catalysis Communications. 2020; 134: 105862.https://doi.org/10.1016/j.catcom.2019.105862

68. Aissaoui N., Bergaoui L., Landoulsi J., Lambert J.-F., Boujday S. Silane Layers on Silicon Surfaces: Mechanism of Interaction, Stability, and Influence on Protein Adsorption. Langmuir. 2012; 28(1): 656–665.https://doi.org/10.1021/la2036778

69. Chitra K., Annadurai G. Fluorescent Silica Nanoparticles in the Detection and Control of the Growth of Pathogen. Journal of Nanotechnology. 2013; 2013: 509628.https://doi.org/10.1155/2013/509628

70. Lapin N.A., Chabal Y.J. Infrared Characterization of Biotinylated Silicon Oxide Surfaces, Surface Stability, and Specific Attachment of Streptavidin. The Journal of Physical Chemistry B. 2009; 113(25): 8776–8783.https://doi.org/10.1021/jp809096m

71. Pasternack R.M., Rivillon Amy S., Chabal Y.J. Attachment of 3-(Aminopropyl)triethoxysilane on Silicon Oxide Surfaces: Dependence on Solution Temperature. Langmuir. 2008; 24(22): 12963–12971.https://doi.org/10.1021/la8024827