Izvestiya of Saratov University.

Physics

ISSN 1817-3020 (Print)
ISSN 2542-193X (Online)

For citation:

Plastun V. O., Saveleva M. S., Gusliakova O. I., Lobanov M. E., Mayorova O. A. Encapsulation in emulsion microgels: A high-tech strategy for the rational use of antibiotics. Izvestiya of Saratov University. Physics , 2024, vol. 24, iss. 3, pp. 228-238. DOI: 10.18500/1817-3020-2024-24-3-228-238, EDN: LCGACH

This is an open access article distributed under the terms of Creative Commons Attribution 4.0 International License (CC-BY 4.0).
Published online: 
30.08.2024
Full text:
download
(downloads: 223)
Language: 
Russian
Heading: 
Biophysics and medical physics
Article type: 
Article
UDC: 
57.089:66.017:665.939.17:577.359
DOI: 
10.18500/1817-3020-2024-24-3-228-238
EDN: 
LCGACH

Encapsulation in emulsion microgels: A high-tech strategy for the rational use of antibiotics

Autors: 
Plastun Valentina O., Saratov State University
Saveleva Mariia Sergeevna, Saratov State University
Gusliakova Olga Igorevna, Saratov State University
Lobanov Mikhail Evgenievich, Saratov State University
Mayorova Oksana Aleksandrovna, Saratov State University
Abstract: 

Background and Objectives: The search of new effective antibacterial drugs and the development of more advanced dosage and delivery systems for existing antibiotics (AB) are actual research objectives for biomedical science. During the study emulsion microgels (EM), based on whey protein isolate, containing antibacterial drugs (cefazolin (CZ), ceftriaxone (CT)) were obtained by ultrasonic homogenization method. The effect of AB-loaded EM on E. coli strain was studied in comparison to free AB. Materials and Methods: The formation of oil-in-water microemulsions stabilized by whey protein isolate (WPI) in saline was carried out using the method of spontaneous emulsification during ultrasonic homogenization using a rod ultrasonic homogenizer. This approach is based on the denaturation of protein under ultrasonic influence on a solution of biomolecules with the subsequent formation of a microgel shell on the surface of oil droplets. Quantitative characteristics of antibiotics loading and its release from microgels were determined spectrophotometrically. Visualization and calculation of EMs particle sizes were carried out using an optical microscope. The study of AB-loaded EM antibacterial action was performed in liquid nutrient media followed by seeding onto nutrient agar. The experiment was followed with live-dead test, carried out by flow cytometry with cell visualization. Results: The rate and characteristics of AB release from the obtained carriers in various model media, as well as the antimicrobial activity of microgels, have been studied. It has been found that the release of AB from synthesized carriers on the first day of the experiment is 10% in all studied model systems. The total amount of AB released over 144 hours reaches 20% in saline solution and 30% in artificial urine. According to the results of the experiment, all samples of EM, containing CZ caused inhibition of E. coli growth within 7 days. Of these, total suppression of bacterial growth was observed within 1 day for EM 1 : 3 and 1 days for EM 1 : 5, on the remaining days – partial growth suppression. Free CZ remained active during the first day. EM, containing CT, demonstrated an antibacterial effect for 14 days. In this case, the bactericidal nature of the action was observed within 10 days for EM 1 : 3 and 13 days for EM 1 : 5. Free CT also had an antimicrobial effect for 14 days, but the duration of the period of complete growth inhibition in all control samples was significantly shorter compared to EM samples. Conclusion: The immobilization of antibacterial drugs (CZ, CT) into emulsion microgels not only does not lead to a decrease in their effectiveness, but also makes it possible to significantly increase the duration and intensity of action of these drugs. The results obtained are of interest for further study of the possibilities of using emulsion MGs based on WMB as carriers of antibacterial drugs.

Key words: 
antibiotics
cephalosporins
emulsion microgels
whey protein isolate
Acknowledgments: 
The study was supported by the Russian Science Foundation (project No. 21-75-10042, https://rscf.ru/project/21-75-10042/).
Reference: 
  1. Larsson D. G. J., Flach C.-F. Antibiotic resistance in the environment. Nat. Rev. Microbiol., 2022, vol. 20, pp. 257–269. https://doi.org/10.1038/s41579-021-00649-x
  2. Frieri M., Kumar K., Boutin A. Antibiotic resistance. J. Infect. Public Health, 2017, vol. 10, pp. 369–378. https://doi.org/10.1016/j.jiph.2016.08.007
  3. Khameneh B., Diab R., Ghazvini K., Fazly Bazzaz B. S. Breakthroughs in bacterial resistance mechanisms and the potential ways to combat them. Microb. Pathog., 2016, vol. 95, pp. 32–42. https://doi.org/10.1016/j.micpath.2016.02.009
  4. French G. Clinical impact and relevance of antibiotic resistance. Adv. Drug Deliv. Rev., 2005, vol. 57, pp. 1514–1527. https://doi.org/10.1016/j.addr.2005.04.005
  5. Elder D. P., Kuentz M., Holm R. Antibiotic Resistance: The Need For a Global Strategy. J. Pharm. Sci., 2016, vol. 105, pp. 2278–2287. https://doi.org/10.1016/j.xphs.2016.06.002
  6. Zemlyanko O. M., Rogoza T. M., Zhouravleva G. A. Mechanisms of bacterial multiresistance to antibiotics. Ecol. Genet., 2018, vol. 16, pp. 4–17. https://doi.org/10.17816/ecogen1634-17
  7. Kot B. Antibiotic Resistance Among Uropathogenic Escherichia coli. Polish J. Microbiol., 2019, vol. 68, pp. 403–415. https://doi.org/10.33073/pjm-2019-048
  8. Cao D., Shen Y., Huang Y., Chen B., Chen Z., Ai J., Liu L., Yang L., Wei Q. Levofloxacin Versus Ciprofloxacin in the Treatment of Urinary Tract Infections: Evidence-Based Analysis. Front. Pharmacol., 2021, vol. 12, article no. 658095. https://doi.org/10.3389/fphar.2021.658095
  9. Wang S. S., Ratliff P. D., Judd W. R. Retrospective review of ceftriaxone versus levofloxacin for treatment of E. coli urinary tract infections. Int. J. Clin. Pharm., 2018, vol. 40, pp. 143–149. https://doi.org/10.1007/s11096-017-0560-1
  10. Bunduki G. K., Heinz E., Phiri V. S., Noah P., Feasey N., Musaya J. Virulence factors and antimicrobial resistance of uropathogenic Escherichia coli (UPEC) isolated from urinary tract infections: A systematic review and metaanalysis. BMC Infect. Dis., 2021, vol. 21, pp. 753. https://doi.org/10.1186/s12879-021-06435-7
  11. Jones R. N., Nguyen H. M. 1453. Cephalexin and Cefadroxil Are Not Therapeutic Equivalents for Uncomplicated Cystitis (uUTI): Further Analysis of Cefazolin Surrogate Susceptibility Testing Criteria. Open Forum Infection Diseases, 2019, vol. 6, pp. S530–S531. https://doi.org/10.1093/ofid/ofz360.1317
  12. Nordstöm R., Nystöm L., Ilyas H., Atreya H. S., Borro B. C., Bhunia A., Malmsten M. Microgels as carriers of antimicrobial peptides – Effects of peptide PEGylation. Colloids Surfaces A: Physicochem. Eng. Asp., 2019, vol. 565, pp. 8–15. https://doi.org/10.1016/j.colsurfa.2018.12.049
  13. Xiao X., Ji J., Wang H., Nangia S., Wang H., Libera M. Self-Defensive Antimicrobial Surfaces Using Polymyxin-Loaded Poly(styrene sulfonate) Microgels. ACS Biomater. Sci. Eng., 2022, vol. 8, pp. 4827–4837. https://doi.org/10.1021/acsbiomaterials.2c00783
  14. Cheng H., Liu H., Shi Z., Xu Y., Lian Q., Zhong Q., Liu Q., Chen Y., Pan X., Chen R., Wang P., Gao J., Gao C., Zhang Y., Yue K., Wang J., Shi Z. Long-term antibacterial and biofilm dispersion activity of an injectable in situ crosslinked co-delivery hydrogel/microgel for treatment of implant infection. Chem. Eng. J., 2022, vol. 433, article no. 134451. https://doi.org/10.1016/j.cej.2021.134451
  15. Ma Q., Ma S., Liu J., Pei Y., Tang K., Qiu J., Wan J., Zheng X., Zhang J. Preparation and application of natural protein polymer-based Pickering emulsions. E-Polymers, 2023, vol. 23, article no. 20230001. https://doi.org/10.1515/epoly-2023-0001
  16. Kuznetsov V. A., Kushchev P. O., Ostankova I. V., Pulver A. Y., Pulver N. A., Pavlovich S. V., Poltavtseva R. A. Modern Approaches to the Medical Use of pH- and Temperature-Sensitive Copolymer Hydrogels (Review). Kondens. Sredy i Mezhfaznye Granitsy = Condens. Matter Interphases, 2020, vol. 22, pp. 417–429. https://doi.org/10.17308/kcmf.2020.22/3113
  17. Zheng J., Zhu C., Xu X., Wang X., Fu J. Supramolecular assemblies of multifunctional microgels for biomedical applications. J. Mater. Chem. B, 2023, vol. 11, pp. 6265–6289. https://doi.org/10.1016/j.colsurfa.2018.12.049
  18. Sahiner N. Amino acid-derived poly(L -Lysine) (p(LL)) microgel as a versatile biomaterial: Hydrolytically degradable, drug carrying, chemically modifiable and antimicrobial material. Polym. Adv. Technol., 2020, vol. 31, pp. 2152–2160. https://doi.org/10.1039/D3TB00346A
  19. Saveleva M. S., Lobanov M. E., Gusliakova O. I., Plastun V. O., Prikhozhdenko E. S., Sindeeva O. A., Gorin D. A., Mayorova O. A. Mucoadhesive Emulsion Microgels for Intravesical Drug Delivery: Preparation, Retention at Urothelium, and Biodistribution Study. ACS Appl. Mater. Interfaces, 2023, vol. 15, no. 21, pp. 25354–25368. https://doi.org/10.1021/acsami.3c02741
  20. Schneider C. A., Rasband W. S., Eliceiri K. W. NIH Image to ImageJ: 25 years of image analysis. Nat. Methods, 2012, vol. 9, pp. 671–675. https://doi.org/10.1002/pat.4936
  21. Abu T. M. M., Ghithan J., Abu-Taha M. I., Darwish S. M., Abu-hadid M. M. Spectroscopic approach of the interaction study of ceftriaxone and human serum albumin. J. Biophys. Struct. Biol., 2014, vol. 6, pp. 1–12. https://doi.org/10.1021/acsami.3c02741
  22. Watanabe Y., Hayashi T., Takada R., Yasuda T., Saikawa I., Shimizu K. Studies on protein binding of antibiotics. I. Effect of cefazolin on protein binding and pharmacokinetics of cefoperazone. J. Antibiot. (Tokyo), 1980, vol. 33, pp. 625–635. https://doi.org/10.1038/nmeth.2089
  23. Shimizu T. Studies on protein binding of cefazolin and other antibiotics. Jpn. J. Antibiot., 1974, vol. 27, pp. 296–301. https://doi.org/10.1128/aac.01170-18
  24. Donnelly R. F. Stability of cefazolin sodium in polypropylene syringes and polyvinylchloride minibags. Can. J. Hosp. Pharm., 2011, vol. 64, pp. 241–245. https://doi.org/10.4212/cjhp.v64i4.1035
Received: 
15.03.2024
Accepted: 
03.06.2024
Published: 
30.08.2024
  • 487 reads