Izvestiya of Saratov University.

Physics

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

For citation:

Mayorova O. A., Gusliakova O. I., Saveleva M. S., Kulikov O. A., Inozemtseva O. A. Microgels containing whey protein as a new way of treating bladder and renal diseases. Izvestiya of Saratov University. Physics , 2025, vol. 25, iss. 1, pp. 76-85. DOI: 10.18500/1817-3020-2025-25-1-76-85, EDN: MATQYP

This is an open access article distributed under the terms of Creative Commons Attribution 4.0 International License (CC-BY 4.0).
Published online: 
31.03.2025
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Language: 
Russian
Heading: 
Biophysics and medical physics
Article type: 
Article
UDC: 
57.089:66.017:665.939.17:577.359
DOI: 
10.18500/1817-3020-2025-25-1-76-85
EDN: 
MATQYP

Microgels containing whey protein as a new way of treating bladder and renal diseases

Autors: 
Mayorova Oksana Aleksandrovna, Saratov State University
Gusliakova Olga Igorevna, Saratov State University
Saveleva Mariia Sergeevna, Saratov State University
Kulikov Oleg A., National Research Ogarev Mordovia State University
Inozemtseva Olga Aleksandrovna, Saratov State University
Abstract: 

Background and Objectives: This study covers the biophysical aspects of the use of emulsion microgels stabilized with whey protein isolate (WPI) for targeted drug delivery to the urinary system. Emulsion microgels were prepared by the ultrasonic homogenization method which leads to denaturation of the WPI adsorbed on the water-oil interface and formation of WPI microgel layer at the oil droplet. Materials and Methods: The study of the release profile of the model substance Cyanine 7 immobilized in emulsion microgels has demonstrated a prolonged pattern over 72 hours. The effect of emulsion microgels on the viability of various cell cultures (normal fibroblasts (L929), kidney cells (Hek239), renal carcinoma (Renca) and bladder carcinoma (T24)) has been studied, which has shown a dependence of the cytotoxicity level on the cell type. The Hek239 cells have demonstrated particularly increased sensitivity to emulsion microgels. Results: The accumulation and distribution behaviour of emulsion microgels in laboratory mice have also been studied depending on the route of their administration: intravesical or intravenous. The efficiency of targeting the microgels for urinary system components of the urinary system (kidney or bladder) has been assessed by biodistribution using in vivo fluorescence imaging. Systemic administration has demonstrated selective accumulation not only in the liver but also in the kidneys. Intravesical administration has made it possible to maintain a high local concentration of Cyanine 7 in the bladder at least during 2 h. Histological analysis has validated the safety of WPI-based microgels for delivery into the bladder and kidney. Conclusions: The presented delivery system based on the developed emulsion microgels opens up new prospects for the treatment of diseases of the urinary system using both systemic administration and minimally invasive intravesical instillations.

Key words: 
intravesical instillation; urinary system; whey protein isolate; drug delivery systems; emulsion microgels
Acknowledgments: 
The research was supported by the Russian Science Foundation (project No. 21-75-10042).
Reference: 
  1. Kolman K. B. Cystitis and Pyelonephritis. Prim. Care Clin. Off. Pract., 2019, vol. 46, pp. 191–202. https://doi.org/10.1016/j.pop.2019.01.001
  2. Jansåker F., Li X., Vik I., Frimodt-Møller N., Knudsen J. D., Sundquist K. The Risk of Pyelonephritis Following Uncomplicated Cystitis: A Nationwide Primary Healthcare Study. Antibiotics, 2022, vol. 11, iss. 12, art. 1695. https://doi.org/10.3390/antibiotics11121695
  3. Jhamb M., Lin J., Ballow R., Kamat A. M., Grossman H. B., Wu X. Urinary tract diseases and bladder cancer risk: A case-control study. Cancer Causes Control, 2007, vol. 18, pp. 839–845. https://doi.org/10.1007/s10552-007-9028-2
  4. Kantor F., Hartge P., Hoover R. N., Narayana A. S., Sullivan J. W., Fraumeni J. F. Urinary tract infection and risk of bladder cancer. Am. J. Epidemiol., 1984, vol. 119, pp. 510–515. https://doi.org/10.1093/oxfordjournals.aje.a113768
  5. Maisonneuve P., Agodoa L., Gellert R., Stewart J. H., Buccianti G., Lowenfels A. B., Wolf R. A., Jones E., Dsiney A. P., Briggs D., McCredie M., Boyle P. Cancer in patients on dialysis for end-stage renal disease: An international collaborative study. Lancet, 1999, vol. 354, pp. 93–99. https://doi.org/10.1016/S0140-6736(99)06154-1
  6. Gupta K., Hooton T. M., Naber K. G., Wullt B., Colgan R., Miller L. G., Moran G. J., Nicolle L. E., Raz R., Schaeffer A. J., Soper D. E. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin. Infect. Dis., 2011, vol. 52, pp. e103–e120. https://doi.org/10.1093/cid/ciq257
  7. Rădulescu A., Mădan V., Aungurenci A., Bratu O., Farcaș C., Dinu M., Mischianu D. Antibiotic resistant urinary tract infections in an urology ward. Rom. J. Mil. Med., 2015, vol. 118, pp. 20–22.
  8. Pietrucha-Dilanchian P., Hooton T. M. Diagnosis, Treatment, and Prevention of Urinary Tract Infection. Microbiol. Spectr., 2016, vol. 4, no. 6, art. uti-0021-2015. https://doi.org/10.1128/microbiolspec.UTI-0021-2015
  9. Kallen A. J., Welch H. G., Sirovich B. E. Current Antibiotic Therapy for Isolated Urinary Tract Infections in Women. Arch. Intern. Med., 2006, vol. 166, iss. 6, pp. 635–639. https://doi.org/10.1001/archinte.166.6.635
  10. Hsu C., Chuang Y., Chancellor M. B. Intravesical drug delivery for dysfunctional bladder. Int. J. Urol., 2013, vol. 20, pp. 552–562. https://doi.org/10.1111/iju.12085
  11. Ramakrishnan V. M., Eswara J. R. Basic Bladder Physiology and Anatomy. In: Stiffel J. T., Dray E. V., eds. Urological Care for Patients with Progressive Neurological Conditions. Cham, Springer, 2020, pp. 7–15. https://doi.org/10.1007/978-3-030-23277-1_2
  12. Min G., Zhou G., Schapira M., Sun T.-T., Kong X.-P. Structural basis of urothelial permeability barrier function as revealed by Cryo-EM studies of the 16 nm uroplakin particle. J. Cell Sci., 2003, vol. 116, pp. 4087–4094. https://doi.org/10.1242/jcs.00811
  13. Irwin D. E., Kopp Z. S., Agatep B., Milsom I., Abrams P. Worldwide prevalence estimates of lower urinary tract symptoms, overactive bladder, urinary incontinence and bladder outlet obstruction. BJU Int., 2011, vol. 108, pp. 1132–1138. https://doi.org/10.1111/j.1464-410X.2010.09993.x
  14. Tyagi P., Tyagi S., Kaufman J., Huang L., Miguel F. de Local Drug Delivery to Bladder Using Technology Innovations. Urol. Clin. North Am., 2006, vol. 33, pp. 519–530. https://doi.org/10.1016/j.ucl.2006.06.012
  15. Fang J., Wu P., Fang C., Chen C. Intravesical delivery of 5‐aminolevulinic acid from water‐in‐oil nano/submicron‐emulsion systems. J. Pharm. Sci., 2010, vol. 99, pp. 2375–2385. https://doi.org/10.1002/jps.22006
  16. 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, iss. 21, pp. 25354–25368. https://doi.org/10.1021/acsami.3c02741
  17. Chen T.-Y., Tai Y.-Y., Chang L.-C., Wu P.-C. Fabrication, optimisation and evaluation of cisplatin-loaded nanostructured carriers for improved urothelium permeability for intravesical administration. J. Microencapsul., 2021, vol. 38, pp. 405–413. https://doi.org/10.1080/02652048.2021.1957037
  18. Cannon J. B., Shi Y., Gupta P. Emulsions, microemulsions, and lipid-based drug delivery systems for drug solubilization and delivery–Part I: Parenteral applications. In: Liu R., ed. Water-insoluble drug formulation. CRC Press, 2018, pp. 211–245. https://doi.org/10.1201/9781315120492-10
  19. Singh Y., Meher J. G., Raval K., Khan F. A., Chaurasia M., Jain N. K., Chourasia M. K. Nanoemulsion: Concepts, development and applications in drug delivery. J. Control. Release, 2017, vol. 252, pp. 28–49. https://doi.org/10.1016/j.jconrel.2017.03.008
  20. Simovic S., Prestidge C. A. Nanoparticle layers controlling drug release from emulsions. Eur. J. Pharm. Biopharm., 2007, vol. 67, pp. 39–47. https://doi.org/10.1016/j.ejpb.2007.01.011
  21. Buyukozturk F., Benneyan J. C., Carrier R. L. Impact of emulsion-based drug delivery systems on intestinal permeability and drug release kinetics. J. Control. Release, 2010, vol. 142, pp. 22–30. https://doi.org/10.1016/j.jconrel.2009.10.005
  22. Ming Y., Xia Y., Ma G. Aggregating particles on the O/W interface: Tuning Pickering emulsion for the enhanced drug delivery systems. Aggregate, 2022, vol. 3, iss. 2, art. e162. https://doi.org/10.1002/agt2.162
  23. Tyagi P., Wu P.-C., Chancellor M., Yoshimura N., Huang L. Recent Advances in Intravesical Drug/Gene Delivery. Mol. Pharm., 2006, vol. 3, pp. 369–379. https://doi.org/10.1021/mp060001j
  24. 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/10.1038/nmeth.2089
  25. Animal Cell Culture Guide. Available at: https://www.atcc.org/resources/culture- guides/animal- cell-culture-guide (accessed September 1, 2024).
  26. Ostojić S., Pavlović M., Živić M., Filipović Z., Gorjanović S., Hranisavljević S., Dojčinović M. Processing of whey from dairy industry waste. Environ. Chem. Lett., 2005, vol. 3, pp. 29–32. https://doi.org/10.1007/s10311-005-0108-9
  27. Armetha V., Hariyadi P., Sitanggang A. B., Yuliani S. The stability of whey protein-stabilized red palm oil emulsion from a rheological perspective. Ann. Univ. Dunarea Jos Galati. Fascicle VI – Food Technol., 2022, vol. 46, pp. 35–49. https://doi.org/10.35219/foodtechnology.2022.2.03
  28. Standard I. Biological evaluation of medical devices – Part 5: Tests for in vitro cytotoxicity. Geneve, Switzerland, International Organization for Standardization, 2023, pp. 1–11.
  29. Sakaeda T., Hirano K. O/W Lipid Emulsions for Parenteral Drug Delivery. III. Lipophilicity Necessary for Incorporation in Oil Particles Even After Intravenous Injection. J. Drug Target., 1998, vol. 6, pp. 119–127. https://doi.org/10.3109/10611869808997887
  30. Hippalgaonkar K., Majumdar S., Kansara V. Injectable Lipid Emulsions–Advancements, Opportunities and Challenges. AAPS PharmSciTech, 2010, vol. 11, pp. 1526–1540. https://doi.org/10.1208/s12249- 010-9526-5
  31. Chansri N., Kawakami S., Yamashita F., Hashida M. Inhibition of liver metastasis by all-trans retinoic acid incorporated into O/W emulsions in mice. Int. J. Pharm., 2006, vol. 321, pp. 42–49. https://doi.org/10.1016/j.ijpharm.2006.05.008
  32. Huang X., Ma Y., Li Y., Han F., Lin W. Targeted Drug Delivery Systems for Kidney Diseases. Front. Bioeng. Biotechnol., 2021, vol. 9, art. 683247. https://doi.org/10.3389/fbioe.2021.683247
  33. Minamiguchi K., Tanaka T., Nishiofuku H., Fukuoka Y., Taiji R., Matsumoto T., Saito N., Taguchi H., Marugami N., Hirai T., Kichikawa K. Comparison of embolic effect between water‐in‐oil emulsion and microspheres in transarterial embolization for rat hepatocellular carcinoma model. Hepatol. Res., 2020, vol. 50, pp. 1297–1305. https://doi.org/10.1111/hepr.13561
  34. Tao S., Lin B., Zhou H., Sha S., Hao X., Wang X., Chen J., Zhang Y., Pan J., Xu J., Zeng J., Wang Y., He X., Huang J., Zhao W., Fan J.-B. Janus particle-engineered structural lipiodol droplets for arterial embolization. Nat. Commun., 2023, vol. 14, art. 5575. https://doi.org/10.1038/s41467-023-41322-6
Received: 
12.05.2024
Accepted: 
02.09.2024
Published: 
31.03.2025
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